Immune-based therapies.

PubMed

Lein, B

1995-12-01

Several immune-based HIV therapy studies presented at the Interscience Conference on Antimicrobial Agents Chemotherapy (ICAAC) are summarized. These studies involve the following therapies: HIV-IT, a gene therapy approach to augmenting the body's anti-HIV responses; interferon-alpha n3, a new formulation of alpha interferon with fewer toxicities; transfer of immune responses from one individual to another, also called passive immune therapy; and interleukin-2 (IL-2) in combination with protease inhibitors.

Association of Delayed Antimicrobial Therapy with One-Year Mortality in Pediatric Sepsis.

PubMed

Han, Moonjoo; Fitzgerald, Julie C; Balamuth, Fran; Keele, Luke; Alpern, Elizabeth R; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert W; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L

2017-07-01

Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with 1-year mortality in pediatric severe sepsis. Retrospective observational study. Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013. One hundred sixty patients aged ≤21 years treated for severe sepsis. None. We tested the association of hourly delays from sepsis recognition to antimicrobial administration with 1-year mortality using multivariable Cox and logistic regression. Overall 1-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137 min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3 h were not associated with 1-year mortality. However, increased 1-year mortality was evident in patients who received antimicrobials ≤1 h (aOR 3.8, 95% CI 1.2, 11.7) or >3 h (aOR 3.5, 95% CI 1.3, 9.8) compared with patients who received antimicrobials within 1 to 3 h from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ≤1 h was also associated with increased 1-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy >3 h was not associated with 1-year mortality (aOR 2.2, 95% CI 0.5, 11.0). Hourly delays to antimicrobial therapy, up to 3 h, were not associated with 1-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ≤1 h from sepsis recognition was associated with increased 1-year mortality should be regarded as hypothesis-generating for future studies.

[Antimicrobial treatment in complicated intraabdominal infections--current situation].

PubMed

Vyhnánek, F

2009-04-01

Compared to other infections, intraabdominal infections include wide spectrum of infections of various severity, have different ethiology, which is frequently polymicrobial, show different microbiological results, which are difficult to interpret. The role of surgical intervention is essential. Intraabdominal infections are common causes of morbidity and mortality. Their prognosis is significantly improved with early and exact diagnosis, appropriate surgical or radiological intervention and timely effective antimicrobial therapy. Practitioners may choose between older or more modern antibiotics, between monotherapy or combination therapy, however, they should also consider clinical condition of the patient, the antibiotic's spectrum of activity, the treatment timing and its duration, the dose and dosing scheme of the particular antimicrobials. Furthermore, antimicrobial therapy should be used with caution, with the aim to prevent development of antimicrobial resistence. Inappropriate choice of antimicrobials in initial empiric therapy results in relapsing infections, surgical intervention and prolongation of hospitalization, and even death rates reflect adequate and timely empiric therapy.

Challenges in assessing nursing home residents with advanced dementia for suspected urinary tract infections.

PubMed

D'Agata, Erika; Loeb, Mark B; Mitchell, Susan L

2013-01-01

To describe the presentation of suspected urinary tract infections (UTIs) in nursing home (NH) residents with advanced dementia and how they align with minimum criteria to justify antimicrobial initiation. Twelve-month prospective study. Twenty-five NHs. Two hundred sixty-six NH residents with advanced dementia. Charts were abstracted monthly for documentation of suspected UTI episodes to determine whether episodes met minimum criteria to initiate antimicrobial therapy according to consensus guidelines. Seventy-two residents experienced 131 suspected UTI episodes. Presenting symptoms and signs for these episodes are mental status change (44.3%), fever (20.6%), hematuria (6.9%), dysuria (3.8%), costovertebral tenderness (2.3%), urinary frequency (1.5%), rigor (1.5%), urgency (0%), and suprapubic pain (0%). Only 21 (16.0%) episodes met minimal criteria to initiate antimicrobial therapy based on signs and symptoms. Of the 110 episodes that lacked minimum criteria to justify antimicrobial initiation, 82 (74.5%) were treated with antimicrobial therapy. Urinalyses and urine culture results were available for 101 episodes, of which 80 (79.2%) had positive results on both tests. The proportion of episodes with a positive urinalysis and culture was similar for those that met (83.3%) and did not meet (78.3%) minimum criteria (P = .06). The symptoms and signs necessary to meet minimum criteria to support antimicrobial initiation for UTIs are frequently absent in NH residents with advanced dementia. Antimicrobial therapy is prescribed for the majority of suspected UTIs that do not meet these minimum criteria. Urine specimens are frequently positive regardless of symptoms. These observations underscore the need to reconsider the diagnosis and the initiation of treatment for suspected UTIs in advanced dementia. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

Understanding antimicrobial stewardship: Disease severity treatment thresholds and antimicrobial alternatives among organic and conventional calf producers.

PubMed

Habing, Greg; Djordjevic, Catherine; Schuenemann, Gustavo M; Lakritz, Jeff

2016-08-01

Reductions in livestock antimicrobial use (AMU) can be achieved through identification of effective antimicrobial alternatives as well as accurate and stringent identification of cases requiring antimicrobial therapy. Objective measurements of selectivity that incorporate appropriate case definitions are necessary to understand the need and potential for reductions in AMU through judicious use. The objective of this study was to measure selectivity using a novel disease severity treatment threshold for calf diarrhea, and identify predictors of more selective application of antimicrobials among conventional dairy producers. A second objective of this study was to describe the usage frequency and perceptions of efficacy of common antimicrobial alternatives among conventional and organic producers. The cross-sectional survey was mailed to Michigan and Ohio, USA dairy producers and contained questions on AMU attitudes, AMU practices, veterinary-written protocols, and antimicrobial alternatives. The treatment threshold, defined based on the case severity where the producer would normally apply antimicrobials, was identified with a series of descriptions with increasing severity, and ordinal multivariable logistic regression was used to determine the association between the treatment threshold and individual or herd characteristics. The response rate was 49% (727/1488). Overall, 42% of conventional producers reported any veterinary-written treatment protocol, and 27% (113/412) of conventional producers had a veterinary-written protocol for the treatment of diarrhea that included a case identification. The majority (58%, 253/437) of conventional producers, but a minority (7%) of organic producers disagreed that antibiotic use in agriculture led to resistant bacterial infections in people. Among conventional producers, the proportion of producers applying antimicrobials for therapy increased from 13% to 67% with increasing case severity. The treatment threshold was low, medium, and high for 11% (47/419), 57% (251/419), and 28% (121/419) of conventional producers, respectively. Treatment threshold was not significantly associated with the use of protocols or frequency of veterinary visits; however, individuals with more concern for the public health impact of livestock AMU had a significantly higher treatment threshold (i.e. more selective) (p<0.05). Alternative therapies were used by both organic and conventional producers, but, garlic, aloe, and "other herbal therapies" with little documented efficacy were used by a majority (>60%) of organic producers. Overall, findings from this study highlight the need for research on antimicrobial alternatives, wider application of treatment protocols, and farm personnel education and training on diagnostic criteria for initiation of antimicrobial therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of formulary restriction with prior authorization by an antimicrobial stewardship program

PubMed Central

Reed, Erica E.; Stevenson, Kurt B.; West, Jessica E.; Bauer, Karri A.; Goff, Debra A.

2013-01-01

In an era of increasing antimicrobial resistance and few antimicrobials in the developmental pipeline, many institutions have developed antimicrobial stewardship programs (ASPs) to help implement evidence-based (EB) strategies for ensuring appropriate utilization of these agents. EB strategies for accomplishing this include formulary restriction with prior authorization. Potential limitations to this particular strategy include delays in therapy, prescriber pushback, and unintended increases in use of un-restricted antimicrobials; however, our ASP found that implementing prior authorization for select antimicrobials along with making a significant effort to educate clinicians on criteria for use ensured more appropriate prescribing of these agents, hopefully helping to preserve their utility for years to come. PMID:23154323

Impact of formulary restriction with prior authorization by an antimicrobial stewardship program.

PubMed

Reed, Erica E; Stevenson, Kurt B; West, Jessica E; Bauer, Karri A; Goff, Debra A

2013-02-15

In an era of increasing antimicrobial resistance and few antimicrobials in the developmental pipeline, many institutions have developed antimicrobial stewardship programs (ASPs) to help implement evidence-based (EB) strategies for ensuring appropriate utilization of these agents. EB strategies for accomplishing this include formulary restriction with prior authorization. Potential limitations to this particular strategy include delays in therapy, prescriber pushback, and unintended increases in use of un-restricted antimicrobials; however, our ASP found that implementing prior authorization for select antimicrobials along with making a significant effort to educate clinicians on criteria for use ensured more appropriate prescribing of these agents, hopefully helping to preserve their utility for years to come.

Antimicrobial Treatment Options for Granulomatous Mastitis Caused by Corynebacterium Species

PubMed Central

Dobinson, Hazel C.; Anderson, Trevor P.; Chambers, Stephen T.; Doogue, Matthew P.; Seaward, Lois

2015-01-01

Corynebacterium species are increasingly recognized as important pathogens in granulomatous mastitis. Currently, there are no published treatment protocols for Corynebacterium breast infections. This study describes antimicrobial treatment options in the context of other management strategies used for granulomatous mastitis. Corynebacterium spp. isolated from breast tissue and aspirate samples stored from 2002 to 2013 were identified and determined to the species level using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), 16S RNA sequencing, and rpoB gene targets. The MICs for 12 antimicrobials were performed using Etest for each isolate. Correlations of these with antimicrobial characteristics, choice of antimicrobial, and disease outcome were evaluated. Corynebacterium spp. from breast tissue and aspirate samples were confirmed in 17 isolates from 16 patients. Based on EUCAST breakpoints, Corynebacterium kroppenstedtii isolates (n = 11) were susceptible to seven antibiotic classes but resistant to β-lactam antibiotics. Corynebacterium tuberculostearicum isolates (n = 4) were multidrug resistant. Two nonlipophilic species were isolated, Corynebacterium glucuronolyticum and Corynebacterium freneyi, both of which have various susceptibilities to antimicrobial agents. Short-course antimicrobial therapy was common (median, 6 courses per subject; range, 1 to 9 courses). Patients with C. kroppenstedtii presented with a hot painful breast mass and underwent multiple surgical procedures (median, 4 procedures; range, 2 to 6 procedures). The management of Corynebacterium breast infections requires a multidisciplinary approach and includes culture and appropriate sensitivity testing to guide antimicrobial therapy. Established infections have a poor outcome, possibly because adequate concentrations of some drugs will be difficult to achieve in lipophilic granulomata. Lipophilic antimicrobial therapy may offer a therapeutic advantage. The role of immunotherapy has not been defined. PMID:26135858

Antimicrobial Prescribing in Dogs and Cats in Australia: Results of the Australasian Infectious Disease Advisory Panel Survey.

PubMed

Hardefeldt, L Y; Holloway, S; Trott, D J; Shipstone, M; Barrs, V R; Malik, R; Burrows, M; Armstrong, S; Browning, G F; Stevenson, M

2017-07-01

Investigations of antimicrobial use in companion animals are limited. With the growing recognition of the need for improved antimicrobial stewardship, there is urgent need for more detailed understanding of the patterns of antimicrobial use in this sector. To investigate antimicrobial use for medical and surgical conditions in dogs and cats by Australian veterinarians. A cross-sectional study was performed over 4 months in 2011. Respondents were asked about their choices of antimicrobials for empirical therapy of diseases in dogs and cats, duration of therapy, and selection based on culture and susceptibility testing, for common conditions framed as case scenarios: 11 medical, 2 surgical, and 8 dermatological. A total of 892 of the 1,029 members of the Australian veterinary profession that completed the survey satisfied the selection criteria. Empirical antimicrobial therapy was more common for acute conditions (76%) than chronic conditions (24%). Overall, the most common antimicrobial classes were potentiated aminopenicillins (36%), fluoroquinolones (15%), first- and second-generation cephalosporins (14%), and tetracyclines (11%). Third-generation cephalosporins were more frequently used in cats (16%) compared to dogs (2%). Agreement with Australasian Infectious Disease Advisory Panel (AIDAP) guidelines (generated subsequently) was variable ranging from 0 to 69% between conditions. Choice of antimicrobials by Australian veterinary practitioners was generally appropriate, with relatively low use of drugs of high importance, except for the empirical use of fluoroquinolones in dogs, particularly for otitis externa and 3rd-generation cephalosporins in cats. Future surveys will determine whether introduction of the 2013 AIDAP therapeutic guidelines has influenced prescribing habits. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Scaffold-based Anti-infection Strategies in Bone Repair

PubMed Central

Johnson, Christopher T.; García, Andrés J.

2014-01-01

Bone fractures and non-union defects often require surgical intervention where biomaterials are used to correct the defect, and approximately 10% of these procedures are compromised by bacterial infection. Currently, treatment options are limited to sustained, high doses of antibiotics and surgical debridement of affected tissue, leaving a significant, unmet need for the development of therapies to combat device-associated biofilm and infections. Engineering implants to prevent infection is a desirable material characteristic. Tissue engineered scaffolds for bone repair provide a means to both regenerate bone and serve as a base for adding antimicrobial agents. Incorporating anti-infection properties into regenerative medicine therapies could improve clinical outcomes and reduce the morbidity and mortality associated with biomaterial implant-associated infections. This review focuses on current animal models and technologies available to assess bone repair in the context of infection, antimicrobial agents to fight infection, the current state of antimicrobial scaffolds, and future directions in the field. PMID:25476163

Adjunct Antimicrobial Therapy and Periodontal Surgery to Treat Generalized Aggressive Periodontitis: A Case Report.

PubMed

Irokawa, Daisuke; Makino-Oi, Asako; Fujita, Takahisa; Yamamoto, Shigeki; Tomita, Sachiyo; Saito, Atsushi

2016-01-01

Here we report a case of generalized aggressive periodontitis treated with periodontal therapy including adjunct antimicrobial therapy and periodontal surgery. The patient was a 22-year-old woman who presented with the chief complaint of gingival recession. Baseline examination revealed generalized plaque deposition and gingival inflammation. Thirty-nine percent of the sites had a probing depth (PD) of 4-6 mm and 2% a PD of ≥7 mm; 63% exhibited bleeding on probing (BOP). Radiographic examination revealed vertical bone loss in the molars and horizontal bone loss in other teeth. Microbiological examination of subgingival plaque revealed the presence of Aggregatibacter actinomycetemcomitans and Tannerella forsythia. Oral health-related quality of life was assessed as a measure of patient-reported outcome. Based on a clinical diagnosis of generalized aggressive periodontitis, initial periodontal therapy and adjunct antimicrobial therapy were implemented. After reducing inflammation and subgingival bacteria, open flap debridement was performed for teeth with a PD of ≥4 mm. Reevaluation showed no sites with a PD of ≥5 mm, a minimal level of BOP, and a marked reduction in the level of the targeted periodontal pathogens. The patient's oral health-related quality of life was slightly worsened during supportive periodontal therapy (SPT). Implementation of adjunct antimicrobial therapy targeting periodontal pathogens and subsequent periodontal surgery resulted in improvement in periodontal and microbiological parameters. This improvement has been adequately maintained over a 2-year period. However, additional care is necessary to further improve the patient's oral health-related quality of life during SPT.

An alternate pathophysiologic paradigm of sepsis and septic shock

PubMed Central

Kumar, Anand

2014-01-01

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

An evaluation of the association between an antimicrobial stewardship score and antimicrobial usage

PubMed Central

Pakyz, Amy L.; Moczygemba, Leticia R.; Wang, Hui; Stevens, Michael P.; Edmond, Michael B.

2015-01-01

Objectives To determine whether an antimicrobial stewardship ‘intensity’ score predicts hospital antimicrobial usage. Methods An antimicrobial stewardship score for 44 academic medical centres was developed that comprised two main categories: resources (antimicrobial stewardship programme personnel and automated surveillance software) and strategies (preauthorization, audit with intervention and feedback, education, guidelines and clinical pathways, parenteral to oral therapy programmes, de-escalation of therapy, antimicrobial order forms and dose optimization). Multiple regression analyses were used to assess whether the composite score and also the categories were associated with either total or antimicrobial stewardship programme-target antimicrobial use as measured in days of therapy. Results The mean antimicrobial stewardship programme score was 55 (SD 21); the total composite score was not significantly associated with total or target antimicrobial use [estimate –0.49 (95% CI –2.30 to 0.89)], while the category strategies was significantly and negatively associated with target antimicrobial use [–5.91 (95% CI –9.51 to –2.31)]. Conclusions The strategy component of a score developed to measure the intensity of antimicrobial stewardship was associated with the amount of antimicrobials used. Thus, the number and types of strategies employed by antimicrobial stewardship programmes may be of particular importance in programme effectiveness. PMID:25614043

The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

PubMed Central

Carrera, E T; Dias, H B; Corbi, S C T; Marcantonio, R A C; Bernardi, A C A; Bagnato, V S; Hamblin, M R; Rastelli, A N S

2017-01-01

In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications. PMID:29151775

The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

NASA Astrophysics Data System (ADS)

Carrera, E. T.; Dias, H. B.; Corbi, S. C. T.; Marcantonio, R. A. C.; Bernardi, A. C. A.; Bagnato, V. S.; Hamblin, M. R.; Rastelli, A. N. S.

2016-12-01

In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications.

Antimicrobial Effects of Antipyretics.

PubMed

Zimmermann, Petra; Curtis, Nigel

2017-04-01

Antipyretics are some of the most commonly used drugs. Since they are often coadministered with antimicrobial therapy, it is important to understand the interactions between these two classes of drugs. Our review is the first to summarize the antimicrobial effects of antipyretic drugs and the underlying mechanisms involved. Antipyretics can inhibit virus replication, inhibit or promote bacterial or fungal growth, alter the expression of virulence factors, change the surface hydrophobicity of microbes, influence biofilm production, affect the motility, adherence, and metabolism of pathogens, interact with the transport and release of antibiotics by leukocytes, modify the susceptibility of bacteria to antibiotics, and induce or reduce the frequency of mutations leading to antimicrobial resistance. While antipyretics may compromise the efficacy of antimicrobial therapy, they can also be beneficial, for example, in the management of biofilm-associated infections, in reducing virulence factors, in therapy of resistant pathogens, and in inducing synergistic effects. In an era where it is becoming increasingly difficult to find new antimicrobial drugs, targeting virulence factors, enhancing the efficacy of antimicrobial therapy, and reducing resistance may be important strategies. Copyright © 2017 American Society for Microbiology.

Nanoparticle-based Therapies for Wound Biofilm Infection: Opportunities and Challenges

PubMed Central

Kim, Min-Ho

2016-01-01

Clinical data from human chronic wounds implicates biofilm formation with the onset of wound chronicity. Despite the development of novel antimicrobial agents, the cost and complexity of treating chronic wound infections associated with biofilms remain a serious challenge, which necessitates the development of new and alternative approaches for effective anti-biofilm treatment. Recent advancement in nanotechnology for developing a new class of nanoparticles that exhibit unique chemical and physical properties holds promise for the treatment of biofilm infections. Over the last decade, nanoparticle-based approaches against wound biofilm infection have been directed toward developing nanoparticles with intrinsic antimicrobial properties, utilizing nanoparticles for controlled antimicrobials delivery, and applying nanoparticles for antibacterial hyperthermia therapy. In addition, a strategy to functionalize nanoparticles towards enhanced penetration through the biofilm matrix has been receiving considerable interest recently by means of achieving an efficient targeting to the bacterial cells within biofilm matrix. This review summarizes and highlights the recent development of these nanoparticle-based approaches as potential therapeutics for controlling wound biofilm infection, along with current challenges that need to be overcome for their successful clinical translation. PMID:26955044

Impact of a pharmacist-driven beta-lactam allergy interview on inpatient antimicrobial therapy: A pilot project.

PubMed

Sigona, Nicholas S; Steele, Jeffrey M; Miller, Christopher D

To determine the impact of a pharmacist-driven beta-lactam allergy interview on antimicrobial therapy. Tertiary care academic medical center. Clarification of beta-lactam allergy may expand treatment options for patients and potentially improve outcomes, reduce toxicity, and reduce costs. At our institution, a pilot service using a pharmacy resident and infectious diseases clinical pharmacist was implemented to clarify beta-lactam allergy information and, where appropriate, recommend a change to the patient's antibiotic therapy. Adult patients with a documented beta-lactam allergy who had received non-penicillin antibiotics and who had undergone a beta-lactam allergy interview were identified via pharmacy intervention data. A pharmacist interviewed these patients with the use of an internally developed allergy questionnaire. Recommendations for beta-lactam therapy were made to the patient's primary medical team based on the results of the allergy interview and factors including infection type and culture results. The primary objectives were to determine the percentage of patients successfully switched to beta-lactam therapy as a result of the drug allergy interview, to identify allergy discrepancies between the electronic medical record (EMR) and pharmacist's interview, and to quantify the acceptance rate of the pharmacist's antimicrobial recommendations after drug allergy clarification. Thirty-two patients were interviewed, and 24 were candidates for a beta-lactam recommendation. As a result of the interview, 21 patients (65.6%) were successfully switched from a non-penicillin antibiotic to a cephalosporin, carbapenem, or penicillin. A discrepancy between the EMR-reported allergy and history obtained on interview was identified in 11 patients (34.4%). Medical providers accepted 87.5% of pharmacists' antimicrobial recommendations. A pharmacist-driven beta-lactam allergy interview was effective in switching eligible patients to beta-lactam therapy and identifying discrepancies between EMR-documented allergies and confirmed allergies. Antimicrobial recommendations were well received by medical providers with a high acceptance rate. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Antimicrobial Prescribing Practices Following Publication of Guidelines for the Prevention of Infections Associated With Combat-Related Injuries

PubMed Central

Tribble, David R.; Lloyd, Bradley; Weintrob, Amy; Ganesan, Anuradha; Murray, Clinton K.; Li, Ping; Bradley, William; Fraser, Susan; Warkentien, Tyler; Gaskins, Lakisha J.; Seillier-Moiseiwitsch, Françoise; Millar, Eugene V.; Hospenthal, Duane R.

2018-01-01

Background Timely and limited antibiotic prophylaxis (postinjury antimicrobial therapy) targeting specific traumatic injuries is a well-recognized measure to lessen posttraumatic infection. Modern military combat injuries raise significant challenges because of complex multiple injuries and limited data derived directly from well-controlled trials to base recommendations. Expert consensus review of available evidence led to published guidance for selection and duration of antimicrobial therapy for combat-related trauma infection prevention. This analysis evaluates antibiotic-prescribing practices by military physicians in the operational theater relative to the published guidance. Methods Trauma history and infectious disease-specific inpatient care information is captured through the Joint Theater Trauma Registry along with a supplemental infectious disease module. Injury patterns are classified based on documented International Classification of Diseases-9th Revision codes with a composite assessment of each patient’s injury pattern. Antimicrobial use categorized as prophylaxis is prescribed within the first 48 hours postinjury. Adherence to published guidance is reported along with patient characteristics and injury severity to assess for potential explanations of nonadherence. Results During June to November 2009, 75% of the 610 eligible trauma patients received antimicrobial prophylaxis. Adherence to the recommended antibiotic agent on the day of injury was in the range of 46% to 50% for the most common extremity injury patterns and 10% in penetrating abdominal injuries. Antibiotics were given in 39% of patients sustaining injuries that are recommendations to not receive antimicrobial prophylaxis. Conclusions This first evaluation of combat trauma-related antibiotic prophylaxis shows adherence levels comparable or superior to reported rates in civilian settings despite the austere, frequently mass casualty environment. Areas for interval surveillance and education-based strategies for improved adherence to practice guidance are identified. PMID:21814096

Antimicrobial use in the veterinary cancer patient.

PubMed

Boudreaux, Bonnie

2014-09-01

This article discusses the clinically relevant uses of antimicrobials in small animal cancer patients. The article focuses on general considerations of antimicrobial use, antimicrobials in the neutropenic patient, prophylactic antimicrobial usage, antimicrobials in radiation therapy, and antimicrobials in metronomic chemotherapy protocols. Copyright © 2014 Elsevier Inc. All rights reserved.

Antimicrobials used for surgical prophylaxis by equine veterinary practitioners in Australia.

PubMed

Hardefeldt, L Y; Browning, G F; Thursky, K; Gilkerson, J R; Billman-Jacobe, H; Stevenson, M A; Bailey, K E

2018-01-01

Antimicrobials are widely used in Australian veterinary practices, but no investigation into the classes of antimicrobials used, or the appropriateness of use in horses, has been conducted. The aim of the study was to describe antimicrobial use for surgical prophylaxis in equine practice in Australia. Cross-sectional questionnaire survey. An online questionnaire was used to document antimicrobial usage patterns. Information solicited in the questionnaire included demographic details of the respondents, the frequency with which antimicrobials were used for specific surgical conditions (including the dose, timing and duration of therapy) and practice antimicrobial use policies and sources of information about antimicrobials and their uses. A total of 337 members of the Australian veterinary profession completed the survey. Generally, the choice of antimicrobial was appropriate for the specified equine surgical condition, but the dose and duration of therapy varied greatly. While there was poor optimal compliance with British Equine Veterinary Association guidelines in all scenarios (range 1-15%), except removal of a nonulcerated dermal mass (42%), suboptimal compliance (compliant antimicrobial drug selection but inappropriate timing, dose or duration of therapy) was moderate for all scenarios (range 48-68%), except for an uninfected contaminated wound over the thorax, where both optimal and suboptimal compliance was very poor (1%). Veterinarians practicing at a university hospital had higher odds of compliance than general practice veterinarians (Odds ratio 3.2, 95% CI, 1.1-8.9, P = 0.03). Many survey responses were collected at conferences which may introduce selection bias, as veterinarians attending conferences may be more likely to have been exposed to contemporary antimicrobial prescribing recommendations. Antimicrobial use guidelines need to be developed and promoted to improve the responsible use of antimicrobials in equine practice in Australia. An emphasis should be placed on antimicrobial therapy for wounds and appropriate dosing for procaine penicillin. © 2017 EVJ Ltd.

When are Oral Antibiotics a Safe and Effective Choice for Bacterial Bloodstream Infections? An Evidence-Based Narrative Review.

PubMed

Hale, Andrew J; Snyder, Graham M; Ahern, John W; Eliopoulos, George; Ricotta, Daniel; Alston, W Kemper

2018-05-01

Bacterial bloodstream infections (BSIs) are a major cause of morbidity and mortality in the United States. Traditionally, BSIs have been managed with intravenous antimicrobials. However, whether intravenous antimicrobials are necessary for the entirety of the treatment course in BSIs, especially for uncomplicated episodes, is a more controversial matter. Patients that are clinically stable, without signs of shock, or have been stabilized after an initial septic presentation, may be appropriate candidates for treatment of BSIs with oral antimicrobials. There are risks and costs associated with extended courses of intravenous agents, such as the necessity for long-term intravenous catheters, which entail risks for procedural complications, secondary infections, and thrombosis. Oral antimicrobial therapy for bacterial BSIs offers several potential benefits. When selected appropriately, oral antibiotics offer lower cost, fewer side effects, promote antimicrobial stewardship, and are easier for patients. The decision to use oral versus intravenous antibiotics must consider the characteristics of the pathogen, the patient, and the drug. In this narrative review, the authors highlight areas where oral therapy is a safe and effective choice to treat bloodstream infection, and offer guidance and cautions to clinicians managing patients experiencing BSI. © 2018 Society of Hospital Medicine.

Assessment of an intervention aimed at early discontinuation of intravenous antimicrobial therapy in a Brazilian University hospital.

PubMed

Bonella, Gislaine Ferraresi; Fontes, Astrídia Marília de Souza; Jorge, Miguel Tanús; Silveira, Alexandre Barcelos Morais da

2016-01-01

Many interventions demonstrate success in adapting the duration of intravenous antibiotic therapy, but few studies have been conducted in developing countries. The aim of this study was to evaluate the effectiveness of an intervention in the induction of early discontinuation of intravenous antimicrobial therapy and/or its switch to oral therapy. The study employed a before-after intervention design that consisted of displaying a message in the computerized prescription on the third day and suspension of the prescription on the fifth day of intravenous antimicrobial therapy. A total of 465 patients were followed during the control period (CP) and 440 in the intervention period (IP). The intravenous therapy was switched to oral therapy for 11 (2.4%) patients during the CP and 25 (5.7%) in the IP (p=0.011), and was discontinued for 82 (17.6%) patients during the CP and 106 (24.1%) in the IP (p=0.017). During the IP there was a significant increase of patients who had their antimicrobial treatment discontinued before the seventh day of intravenous treatment, 37.40% (49/131) in the IP and 16.13% (15/93) in the CP (p=0.0005). The duration of intravenous antimicrobial therapy decreased by one day, but it was not significant (p=0.136). It is concluded that the proposed intervention is effective in promoting the early discontinuation of antimicrobial treatment and/or switch to oral therapy. As long as a computerized system for prescription already exists, it is easy and inexpensive to be implemented, especially in hospitals in developing countries. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Canine superficial bacterial folliculitis: current understanding of its etiology, diagnosis and treatment.

PubMed

Bloom, Paul

2014-02-01

Superficial bacterial folliculitis (SBF) is more common in the dog than other mammalian species. Until recently, a successful outcome in cases of canine SBF was possible by administering a potentiated amoxicillin, a first generation cephalosporin or a potentiated sulfonamide. Unfortunately, this predictable susceptibility has changed, because methicillin resistant Staphylococcus pseudintermedius (MRSP) and Staphylococcus aureus (MRSA) are becoming more prevalent in canine SBF cases. The increasing frequency of multidrug resistance complicates the selection of antimicrobial therapy. Antimicrobial agents that were once rarely used in cases of canine SBF, such as amikacin, rifampicin and chloramphenicol, are becoming the drugs of choice, based on bacterial culture and susceptibility testing. Furthermore, changes in antimicrobial susceptibility have helped to re-emphasize the importance of a multimodal approach to treatment of the disease, including topical therapy. Due to the increasing frequency of identification of highly resistant Staphylococcus spp., topical antimicrobial therapy, including the use of diluted sodium hypochlorite (bleach), is becoming necessary to successfully treat some cases of canine SBF. Other important antiseptics that can be used include chlorhexidine, benzoyl peroxide, ethyl lactate, triclosan and boric acid/acetic acid. This review discusses the diagnostic and therapeutic management of canine SBF, with a special emphasis on treating methicillin resistant staphylococcal infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antimicrobial Treatment for Systemic Anthrax: Analysis of Cases from 1945 to 2014 Identified Through a Systematic Literature Review.

PubMed

Pillai, Satish K; Huang, Eileen; Guarnizo, Julie T; Hoyle, Jamechia D; Katharios-Lanwermeyer, Stefan; Turski, Theresa K; Bower, William A; Hendricks, Katherine A; Meaney-Delman, Dana

2015-01-01

Systemic anthrax is associated with high mortality. Current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of 2 weeks, bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax, and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. However, in an anthrax mass casualty incident, large numbers of anthrax cases may create challenges in meeting antimicrobial needs. To further inform our understanding of the role of antimicrobials in treating systemic anthrax, a systematic review of the English-language literature was conducted to identify cases of systemic anthrax treated with antimicrobials for which a clinical outcome was recorded. A total of 149 cases of systemic anthrax were identified. Among the identified 59 cases of cutaneous anthrax, 33 were complicated by meningitis (76% mortality), while 26 simply had evidence of the systemic inflammatory response syndrome (4% mortality); 21 of 26 (81%) of this latter group received monotherapy. Subsequent analysis regarding combination antimicrobial therapy was restricted to the remaining 123 cases of more severe anthrax (overall 67% mortality). Recipients of combination bactericidal and protein synthesis inhibitor therapy had a 45% survival versus 28% in the absence of combination therapy (p = 0.07). For meningitis cases (n = 77), survival was greater for those receiving 3 or more antimicrobials over the course of treatment (3 of 4; 75%), compared to receipt of 1 or 2 antimicrobials (12 of 73; 16%) (p = 0.02). Median parenteral antimicrobial duration was 14 days. Combination bactericidal and protein synthesis inhibitor therapy may be appropriate in severe anthrax disease, particularly anthrax meningitis, in a mass casualty incident.

Time-kill kinetic analysis of antimicrobial chemotherapy based on hydrogen peroxide photolysis against Streptococcus mutans biofilm.

PubMed

Shirato, Midori; Nakamura, Keisuke; Kanno, Taro; Lingström, Peter; Niwano, Yoshimi; Örtengren, Ulf

2017-08-01

A recently developed antimicrobial technique utilizing hydroxyl radicals generated by hydrogen peroxide (H 2 O 2 ) photolysis represents a promising new therapy for preventing and treating dental caries. The present study compared the antimicrobial time-kill kinetics of H 2 O 2 photolysis, conventional antiseptics, and antimicrobial photodynamic therapy (aPDT) against biofilm-forming Streptococcus mutans (cariogenic bacteria) grown on hydroxyapatite disks. H 2 O 2 photolysis was performed by irradiating the biofilm immersed in 3% H 2 O 2 with 365-nm light-emitting diode (LED) light at an irradiance of 1000mW/cm 2 for up to 1.5min. Antiseptic treatments consisted of 0.2% chlorhexidine gluconate, 0.5% povidone-iodine, and 3% H 2 O 2 . The biofilm was immersed in each antiseptic for up to 4min. aPDT was performed by irradiating the biofilm immersed in 100μM methylene blue or toluidine blue O with 655-nm laser light at 1000mW/cm 2 for up to 4min. Based on the time-kill assay, the decimal reduction value (D-value) of each treatment was determined. With a D-value of 0.06min, H 2 O 2 photolysis exhibited the highest bactericidal effect against biofilm-forming S. mutans. In contrast, antiseptics and aPDT exerted a slower bactericidal effect, with D-values of 0.9-2.7min. In conclusion, the antimicrobial technique based on H 2 O 2 photolysis using 365-nm LED represents a strong adjunctive chemotherapy for dental caries treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Machine learning: novel bioinformatics approaches for combating antimicrobial resistance.

PubMed

Macesic, Nenad; Polubriaginof, Fernanda; Tatonetti, Nicholas P

2017-12-01

Antimicrobial resistance (AMR) is a threat to global health and new approaches to combating AMR are needed. Use of machine learning in addressing AMR is in its infancy but has made promising steps. We reviewed the current literature on the use of machine learning for studying bacterial AMR. The advent of large-scale data sets provided by next-generation sequencing and electronic health records make applying machine learning to the study and treatment of AMR possible. To date, it has been used for antimicrobial susceptibility genotype/phenotype prediction, development of AMR clinical decision rules, novel antimicrobial agent discovery and antimicrobial therapy optimization. Application of machine learning to studying AMR is feasible but remains limited. Implementation of machine learning in clinical settings faces barriers to uptake with concerns regarding model interpretability and data quality.Future applications of machine learning to AMR are likely to be laboratory-based, such as antimicrobial susceptibility phenotype prediction.

Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides.

PubMed

Lázár, Viktória; Martins, Ana; Spohn, Réka; Daruka, Lejla; Grézal, Gábor; Fekete, Gergely; Számel, Mónika; Jangir, Pramod K; Kintses, Bálint; Csörgő, Bálint; Nyerges, Ákos; Györkei, Ádám; Kincses, András; Dér, András; Walter, Fruzsina R; Deli, Mária A; Urbán, Edit; Hegedűs, Zsófia; Olajos, Gábor; Méhi, Orsolya; Bálint, Balázs; Nagy, István; Martinek, Tamás A; Papp, Balázs; Pál, Csaba

2018-06-01

Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections.

Antimicrobial use on Canadian dairy farms.

PubMed

Saini, V; McClure, J T; Léger, D; Dufour, S; Sheldon, A G; Scholl, D T; Barkema, H W

2012-03-01

Antimicrobial use (AMU) data are critical for formulating policies for containing antimicrobial resistance. The present study determined AMU on Canadian dairy farms and characterized variation in AMU based on herd-level factors such as milk production, somatic cell count, herd size, geographic region and housing type. Drug use data were collected on 89 dairy herds in 4 regions of Canada, Alberta, Ontario, Québec, and the Maritime provinces (Prince Edward Island, New Brunswick, and Nova Scotia) for an average of 540 d per herd. Dairy producers and farm personnel were asked to deposit empty drug containers into specially provided receptacles. Antimicrobial use was measured as antimicrobial drug use rate (ADUR), with the unit being number of animal defined-daily doses (ADD)/1,000 cow-days. Antimicrobial drug use rates were determined at farm, region, and national level. Combined ADUR of all antimicrobial classes was 14.35 ADD/1,000 cow-days nationally. National level ADUR of the 6 most commonly used antimicrobial drug classes, cephalosporins, penicillins, penicillin combinations, tetracyclines, trimethoprim-sulfonamide combinations, and lincosamides were 3.05, 2.56, 2.20, 1.83, 0.87, and 0.84 ADD/1,000 cow-days, respectively. Dairy herds in Ontario were higher users of third-generation cephalosporins (ceftiofur) than in Québec. Alberta dairy herds were higher users of tetracyclines in comparison to Maritimes. Antimicrobial drug use rate was higher via systemic route as compared with intramammary and other routes of administration (topical, oral, and intrauterine). The ADUR of antimicrobials used intramammarily was higher for clinical mastitis treatment than dry cow therapy. For dry cow therapy, penicillin ADUR was greater than ADUR of first-generation cephalosporins. For clinical mastitis treatment, ADUR of intramammary penicillin combinations was greater than ADUR of cephapirin. Herd-level milk production was positively associated with overall ADUR, ADUR of systemically administered ceftiofur, cephapirin administered for dry cow therapy, and pirlimycin administered for clinical mastitis treatment. Herd size and ADUR of systemically administered ceftiofur were also positively associated. In conclusion, β-lactams were most commonly used on Canadian dairy farms. Among antimicrobials of very high importance in human medicine, the use of fluoroquinolones was rare, whereas third-generation cephalosporins and penicillin combinations containing colistin were used very frequently on Canadian dairy farms. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Total duration of antimicrobial therapy in veterans hospitalized with uncomplicated pneumonia: Results of a national medication utilization evaluation.

PubMed

Madaras-Kelly, Karl J; Burk, Muriel; Caplinger, Christina; Bohan, Jefferson G; Neuhauser, Melinda M; Goetz, Matthew Bidwell; Zhang, Rongping; Cunningham, Francesca E

2016-12-01

Practice guidelines recommend the shortest duration of antimicrobial therapy appropriate to treat uncomplicated pneumonia be prescribed to reduce the emergence of resistant pathogens. A national evaluation was conducted to assess the duration of therapy for pneumonia. Retrospective medication utilization evaluation. Thirty Veterans Affairs medical centers. Inpatients discharged with a diagnosis of pneumonia. A manual review of electronic medical records of inpatients discharged with uncomplicated community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP) was conducted. Appropriate CAP therapy duration was defined as at least 5 days, and up to 3 additional days beginning the first day the patient achieved clinical stability criteria; the appropriate HCAP therapy duration was defined as 8 days. The duration of antimicrobial therapy for intravenous (IV) and oral (PO) inpatient administration, PO therapy dispensed upon discharge, Clostridium difficile infection (CDI), hospital readmission, and death rates were measured. Of 3881 pneumonia admissions, 1739 met inclusion criteria (CAP [n = 1195]; HCAP [n = 544]). Overall, 13.9% of patients (CAP [6.9%], HCAP [29.0%]) received therapy duration consistent with guideline recommendations. The median (interquartile range) days of therapy were 4 days (3-6 days), 1 day (0-3 days), and 6 days (4-8 days) for inpatient IV, inpatient PO, and outpatient PO antimicrobials, respectively. CDI was rare but more common in patients who received therapy duration consistent with guidelines. Therapy duration was not associated with the readmission or mortality rate. Antimicrobials were commonly prescribed for a longer duration than guidelines recommend. The majority of excessive therapy was completed upon discharge, identifying the need for strategies to curtail unnecessary use postdischarge. Journal of Hospital Medicine 2015;11:832-839. © 2015 Society of Hospital Medicine. © 2016 Society of Hospital Medicine.

The effects of photodynamic laser therapy in the treatment of marginal chronic periodontitis

NASA Astrophysics Data System (ADS)

Chifor, Radu; Badea, Iulia; Avram, Ramona; Chifor, Ioana; Badea, Mîndra Eugenia

2016-03-01

The aim of this study was to assess the effects of the antimicrobial photodynamic laser therapy performed during the treatment of deep periodontal disease by using 40 MHz high frequency ultrasonography. The periodontal data recorded during the clinical examination before each treatment session were compared with volumetric changes of the gingiva measured on periodontal ultrasound images. The results show a significant decrease of gingival tissue inflammation proved both by a significant decrease of bleeding on probing as well as by a decrease of the gingival tissues volume on sites where the laser therapy was performed. Periodontal tissues that benefit of laser therapy besides classical non-surgical treatment showed a significant clinical improvement of periodontal status. Based on these findings we were able to conclude that the antimicrobial photodynamic laser therapy applied on marginal periodontium has important anti-inflamatory effect. The periodontal ultrasonography is a method which can provide useful data for assessing the volume changes of gingival tissues, allowing a precise monitoring of marginal periodontitis.

Effect of hospitalization and antimicrobial therapy on antimicrobial resistance of colonizing Staphylococcus epidermidis.

PubMed

Knauer, Ariane; Fladerer, Petra; Strempfl, Christina; Krause, Robert; Wenisch, Christoph

2004-07-31

Endogenous infections with multi-resistant S. epidermidis are among the leading causes of nosocomial infections. The effect of hospitalization and antimicrobial therapy on antimicrobial resistance of colonizing staphylococci was determined from swabs of the nose, hand, axilla and groin from 157 patients on one day. Hospitalization for >72 hours, compared with <72 hours, was associated with a higher percentage of isolates resistant to oxacillin (56% versus 19%), gentamicin (40% versus 15%), trimethoprim (36% versus 17%), clindamycin (56% versus 17%), and fusidic acid (20% versus 4%; p < 0.01 for all), but not to rifampicin (6% versus 1%) or fosfomycin (43% versus 34%, p > 0.05 for both). Concurrent antimicrobial therapy resulted in increased resistance to oxacillin (61% versus 28%), gentamicin (43% versus 20%), and clindamycin (60% versus 26%; p < 0.01 for all), but not to trimethoprim (39% versus 23%), fusidic acid (19% versus 9%), rifampicin (6% versus 3%), or fosfomycin (46% versus 38%, p > 0.05 for all). The increase in resistant isolates was not independent, since hospitalization and antimicrobial therapy were correlated (p < 0.001). After adjustment for potential risk factors such as diabetes mellitus, central venous catheters, and hemodialysis, the odds ratio for oxacillin resistance was 2.8-3.6. None of the risk factors showed statistically significant results, except for the presence of neoplastic disease, which had a significant interaction (P=0.035). The within-subgroup odds ratios for patients with and without neoplasm were 4.2 (95% CI, 2.3-5.7) and 2.1 (95% CI, 0.78-3.12), respectively. These results show that hospitalization for more than three days, with or without antimicrobial therapy, and the presence of neoplastic disease are associated with increased antimicrobial resistance in colonizing S. epidermidis.

Antitoxin Treatment of Inhalation Anthrax: A Systematic Review

PubMed Central

Huang, Eileen; Pillai, Satish K.; Bower, William A.; Hendricks, Katherine A.; Guarnizo, Julie T.; Hoyle, Jamechia D.; Gorman, Susan E.; Boyer, Anne E.; Quinn, Conrad P.; Meaney-Delman, Dana

2016-01-01

Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident. PMID:26690378

Antitoxin Treatment of Inhalation Anthrax: A Systematic Review.

PubMed

Huang, Eileen; Pillai, Satish K; Bower, William A; Hendricks, Katherine A; Guarnizo, Julie T; Hoyle, Jamechia D; Gorman, Susan E; Boyer, Anne E; Quinn, Conrad P; Meaney-Delman, Dana

2015-01-01

Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident.

Prevention of Infections Associated with Combat-Related Burn Injuries

DTIC Science & Technology

2011-08-01

morbidity and mortality. This review highlights evidence - based medicine recommendations using military and civilian data to provide the most comprehensive...devitalized tissue, topical antimicrobial therapy, and optimal time to wound coverage. This evidence - based medicine review was produced to support the

Ligand-Doped Copper Oxo-hydroxide Nanoparticles are Effective Antimicrobials

NASA Astrophysics Data System (ADS)

Bastos, Carlos A. P.; Faria, Nuno; Ivask, Angela; Bondarenko, Olesja M.; Kahru, Anne; Powell, Jonathan

2018-04-01

Bacterial resistance to antimicrobial therapies is an increasing clinical problem. This is as true for topical applications as it is for systemic therapy. Topically, copper ions may be effective and cheap antimicrobials that act through multiple pathways thereby limiting opportunities to bacteria for resistance. However, the chemistry of copper does not lend itself to facile formulations that will readily release copper ions at biologically compatible pHs. Here, we have developed nanoparticulate copper hydroxide adipate tartrate (CHAT) as a cheap, safe, and readily synthesised material that should enable antimicrobial copper ion release in an infected wound environment. First, we synthesised CHAT and showed that this had disperse aquated particle sizes of 2-5 nm and a mean zeta potential of - 40 mV. Next, when diluted into bacterial medium, CHAT demonstrated similar efficacy to copper chloride against Escherichia coli and Staphylococcus aureus, with dose-dependent activity occurring mostly around 12.5-50 mg/L of copper. Indeed, at these levels, CHAT very rapidly dissolved and, as confirmed by a bacterial copper biosensor, showed identical intracellular loading to copper ions derived from copper chloride. However, when formulated at 250 mg/L in a topically applied matrix, namely hydroxyethyl cellulose, the benefit of CHAT over copper chloride was apparent. The former yielded rapid sustained release of copper within the bactericidal range, but the copper chloride, which formed insoluble precipitates at such concentration and pH, achieved a maximum release of 10 ± 7 mg/L copper by 24 h. We provide a practical formulation for topical copper-based antimicrobial therapy. Further studies, especially in vivo, are merited.

Antimicrobial Treatment for Systemic Anthrax: Analysis of Cases from 1945–2014 Identified through Systematic Literature Review

PubMed Central

Pillai, Satish K.; Huang, Eileen; Guarnizo, Julie; Hoyle, Jamechia; Katharios-Lanwermeyer, Stefan; Turski, Theresa; Bower, William; Hendricks, Katherine; Meaney-Delman, Dana

2015-01-01

Background Systemic anthrax is associated with high mortality. Current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of two weeks; bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax; and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. However, in an anthrax mass casualty incident, large numbers of anthrax cases may create challenges in meeting antimicrobial needs. Methods To further inform our understanding of the role of antimicrobials in treating systemic anthrax, a systematic review of the English language literature was conducted to identify cases of systemic anthrax treated with antimicrobials for which a clinical outcome was recorded. Results A total of 149 cases of systemic anthrax were identified (cutaneous [n=59], gastrointestinal [n=28], inhalation [n=26], primary anthrax meningitis [n=19], multiple routes [n=9], and injection [n=8]). Among the identified 59 cases of cutaneous anthrax, 33 were complicated by meningitis (76% mortality), while 26 simply had evidence of the systemic inflammatory response syndrome (4% mortality); 21 of 26 (81%) of this latter group received monotherapy. Subsequent analysis regarding combination antimicrobial therapy was restricted to the remaining 123 cases of more severe anthrax (overall 67% mortality). Recipients of combination bactericidal and protein synthesis inhibitor therapy had a 45% survival versus 28% in the absence of combination therapy (p = 0.07). For meningitis cases (n=77), survival was greater for those receiving a total of ≥3 antimicrobials over the course of treatment (3 of 4; 75%), compared to receipt of 1 or 2 antimicrobials (12 of 73; 16%) (p = 0.02). Median parenteral antimicrobial duration was 14 days. Conclusion Combination bactericidal and protein synthesis inhibitor therapy may be appropriate in severe anthrax disease, particularly anthrax meningitis, in a mass casualty incident. PMID:26623698

Rapid diagnostic testing for community-acquired pneumonia: can innovative technology for clinical microbiology be exploited?

PubMed

Yu, Victor L; Stout, Janet E

2009-12-01

Two nonsynchronous events have affected the management of community-acquired pneumonia (CAP): spiraling empiricism for CAP and the "golden era" of clinical microbiology. The development of broad-spectrum antibiotics has led to widespread empiric use without ascertaining the etiology of the infecting microbe. Unfortunately, this approach clashes with the second event, which is the advent of molecular-based microbiology that can identify the causative pathogen rapidly at the point of care. The urinary antigen is a most effective rapid test that has allowed targeted therapy for Legionnaire disease at the point of care. The high specificity (> 90%) allows the clinician to administer appropriate anti-Legionella therapy based on a single rapid test; however, its low sensitivity (76%) means that a notable number of cases of Legionnaire disease will go undiagnosed if other tests, especially culture, are not performed. Further, culture for Legionella is not readily available. If a culture is not performed, epidemiologic identification of the source of the bacterium cannot be ascertained by molecular fingerprinting of the patient and the putative source strain. We recommend resurrection of the basic principles of infectious disease, which are to identify the microbial etiology of the infection and to use narrow, targeted antimicrobial therapy. To reduce antimicrobial overuse with subsequent antimicrobial resistance, these basic principles must be applied in concert with traditional and newer tests in the clinical microbiology laboratory.

Evaluating the appropriateness of antimicrobial treatment in hospitalized patients: a comparison of three methods.

PubMed

Reisfeld, S; Assaly, M; Tannous, E; Amarney, K; Stein, M

2018-06-01

Approximately 20-50% of antimicrobial therapy in hospitalized patients is considered inappropriate, which may be associated with increased morbidity and mortality. The best method for evaluation of appropriateness is not well defined. To evaluate the rate of appropriate antimicrobial therapy in a secondary hospital using three different methods, and determine the rate of agreement between the different methods. A point prevalence study included all adult hospitalized patients receiving systemic antimicrobial therapy during 2016, screened on a single day. Clinical, laboratory and therapeutic data were collected from patient files, and appropriateness was rated with a qualitative evaluation by expert opinion. In addition, a quantitative evaluation was performed according to 11 quality indicators (QIs) rated for each patient. A strict definition of appropriateness was fulfilled if six essential QIs were met, and a lenient definition was fulfilled if at least five QIs were met. Agreement between methods was analysed using kappa statistic. Among 106 patients included, rates of appropriateness of antimicrobial therapy ranged from 20% to 75%, depending on the method of evaluation. Very low agreement was found between the strict definition and expert opinion (kappa=0.068), and medium agreement was found between the lenient definition and expert opinion (kappa=0.45). Rates of appropriateness of antimicrobial therapy varied between evaluation methods, with low to moderate agreement between the different methods. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality.

PubMed

Díaz-Martín, Ana; Martínez-González, María Luisa; Ferrer, Ricard; Ortiz-Leyba, Carlos; Piacentini, Enrique; Lopez-Pueyo, Maria Jesus; Martín-Loeches, Ignacio; Levy, Mitchell M; Artigas, Antoni; Garnacho-Montero, José

2012-11-18

Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality. This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT). We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001). β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric therapy in patients with severe sepsis and septic shock. Administering a combination of antimicrobials with different mechanisms of action is associated with decreased mortality.

Basis for selecting optimum antibiotic regimens for secondary peritonitis.

PubMed

Maseda, Emilio; Gimenez, Maria-Jose; Gilsanz, Fernando; Aguilar, Lorenzo

2016-01-01

Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity…). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).

Effectiveness of an early switch from intravenous to oral antimicrobial therapy for lower respiratory tract infection in patients with severe motor intellectual disabilities.

PubMed

Kawamura, Masaru; Hoshina, Takayuki; Ogawa, Masato; Nakamoto, Takato; Kusuhara, Koichi

2018-01-01

An early switch from intravenous to oral antimicrobial therapy is useful for reducing the duration of the hospitalization in adult patients with community acquired-pneumonia, whereas the efficacy of switch therapy for pediatric patients with community acquired (CA)-lower respiratory tract infection (LRTI) is uncertain. The aim of this study is to investigate the efficacy of switch therapy for LRTI in patients with severe motor intellectual disabilities (SMID). This retrospective study was performed on 92 patients with SMID who were admitted to the Department of Pediatrics at the Hospital of University of Occupational and Environmental Health, Japan from April 1, 2010 to March 31, 2017 for the suspicion of bacterial LRTI and were initially treated with an intravenous antimicrobial agent. Clinical outcomes were compared between patients with switch therapy (Switch therapy group) and conventional intravenous antimicrobial therapy (No switch therapy group). Thirteen and 79 in patients with SMID belonged to Switch thrapy group and No switch therapy group, respectively. Length of hospital stay in Switch therapy group was significantly shorter than that in No switch therapy group (P = 0.002). In the patients undergoing switch therapy, there was no patient who required re-treatment and/or re-hospitalization. Switch therapy for LRTI was useful for the reduction of length of hospital stay without increasing risk of re-treatment and re-hospitalization in patients with SMID. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Nanomedicine and advanced technologies for burns: Preventing infection and facilitating wound healing.

PubMed

Mofazzal Jahromi, Mirza Ali; Sahandi Zangabad, Parham; Moosavi Basri, Seyed Masoud; Sahandi Zangabad, Keyvan; Ghamarypour, Ameneh; Aref, Amir R; Karimi, Mahdi; Hamblin, Michael R

2018-01-01

According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally employed to inhibit burn infections followed by a burn wound therapy, because systemic antibiotics have problems in reaching the infected site, coupled with increasing microbial drug resistance. Nanotechnology has provided a range of molecular designed nanostructures (NS) that can be used in both therapeutic and diagnostic applications in burns. These NSs can be divided into organic and non-organic (such as polymeric nanoparticles (NPs) and silver NPs, respectively), and many have been designed to display multifunctional activity. The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing. These include biological based approaches (e.g. immune-based antimicrobial molecules, therapeutic microorganisms, antimicrobial agents, etc.), antimicrobial photo- and ultrasound-therapy, as well as nanotechnology-based wound healing approaches as a revolutionizing area. Thus, we focus on organic and non-organic NSs designed to deliver growth factors to burned skin, and scaffolds, dressings, etc. for exogenous stem cells to aid skin regeneration. Eventually, recent breakthroughs and technologies with substantial potentials in tissue regeneration and skin wound therapy (that are as the basis of burn wound therapies) are briefly taken into consideration including 3D-printing, cell-imprinted substrates, nano-architectured surfaces, and novel gene-editing tools such as CRISPR-Cas. Copyright © 2017 Elsevier B.V. All rights reserved.

Microbial Etiology of Pneumonia: Epidemiology, Diagnosis and Resistance Patterns.

PubMed

Cilloniz, Catia; Martin-Loeches, Ignacio; Garcia-Vidal, Carolina; San Jose, Alicia; Torres, Antoni

2016-12-16

Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity. Despite advances in antimicrobial therapies, microbiological diagnostic tests and prevention measures, pneumonia remains the main cause of death from infectious disease in the world. An important reason for the increased global mortality is the impact of pneumonia on chronic diseases, along with the increasing age of the population and the virulence factors of the causative microorganism. The increasing number of multidrug-resistant bacteria, difficult-to-treat microorganisms, and the emergence of new pathogens are a major problem for clinicians when deciding antimicrobial therapy. A key factor for managing and effectively guiding appropriate antimicrobial therapy is an understanding of the role of the different causative microorganisms in the etiology of pneumonia, since it has been shown that the adequacy of initial antimicrobial therapy is a key factor for prognosis in pneumonia. Furthermore, broad-spectrum antibiotic therapies are sometimes given until microbiological results are available and de-escalation cannot be performed quickly. This review provides an overview of microbial etiology, resistance patterns, epidemiology and microbial diagnosis of pneumonia.

Electroporation enhances antimicrobial photodynamic therapy mediated by the hydrophobic photosensitizer, hypericin, Electroporation enhances antimicrobial photodynamic inactivation

PubMed Central

de Melo, Wanessa de Cássia Martins Antunes; Lee, Alexander N; Perussi, Janice Rodrigues; Hamblin, Michael R.

2013-01-01

The effective transport of photosensitizers (PS) across the membrane and the intracellular accumulation of PS are the most crucial elements in antimicrobial photodynamic therapy (aPDT). However, due to the morphological complexity of Gram-negative bacteria the penetration of PS is limited, especially hydrophobic PS. Electroporation (EP) could increase the effectiveness of aPDT, by promoting the formation of transient pores that enhance the permeability of the bacterial membrane to PS. In this study we evaluated the combination of aPDT mediated by the hydrophobic PS, hypericin and EP (aPDT/EP) against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. These bacteria were exposed to light (590 nm) in the presence of hypericin (4µM), following electroporation. The results showed that aPDT/EP inactivated 3.67 logs more E. coli and 2.65 logs more S. aureus than aPDT alone. Based on these results we suggest that EP can potentiate the aPDT effect. PMID:24284122

Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance.

PubMed

Cosme, Angel; Montes, Milagrosa; Ibarra, Begoña; Tamayo, Esther; Alonso, Horacio; Mendarte, Usua; Lizasoan, Jacobo; Herreros-Villanueva, Marta; Bujanda, Luis

2017-05-14

To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance. A total of 1034 patients infected by Helicobacter pylori ( H. pylori ) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori -resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori -resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. Intention-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naïve patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate. Antimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.

Antimicrobial Stewardship Programs: Comparison of a Program with Infectious Diseases Pharmacist Support to a Program with a Geographic Pharmacist Staffing Model

PubMed Central

Ma, Andrew; Clegg, Daniel; Fugit, Randolph V.; Pepe, Anthony; Goetz, Matthew Bidwell; Graber, Christopher J.

2015-01-01

Background: Stewardship of antimicrobial agents is an essential function of hospital pharmacies. The ideal pharmacist staffing model for antimicrobial stewardship programs is not known. Objective: To inform staffing decisions for antimicrobial stewardship teams, we aimed to compare an antimicrobial stewardship program with a dedicated Infectious Diseases (ID) pharmacist (Dedicated ID Pharmacist Hospital) to a program relying on ward pharmacists for stewardship activities (Geographic Model Hospital). Methods: We reviewed a randomly selected sample of 290 cases of inpatient parenteral antibiotic use. The electronic medical record was reviewed for compliance with indicators of appropriate antimicrobial stewardship. Results: At the hospital staffed by a dedicated ID pharmacist, 96.8% of patients received initial antimicrobial therapy that adhered to local treatment guidelines compared to 87% of patients at the hospital that assigned antimicrobial stewardship duties to ward pharmacists (P < .002). Therapy was modified within 24 hours of availability of laboratory data in 86.7% of cases at the Dedicated ID Pharmacist Hospital versus 72.6% of cases at the Geographic Model Hospital (P < .03). When a patient’s illness was determined not to be caused by a bacterial infection, antibiotics were discontinued in 78.0% of cases at the Dedicated ID Pharmacist Hospital and in 33.3% of cases at the Geographic Model Hospital (P < .0002). Conclusion: An antimicrobial stewardship program with a dedicated ID pharmacist was associated with greater adherence to recommended antimicrobial therapy practices when compared to a stewardship program that relied on ward pharmacists. PMID:26405339

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

PubMed

Sartelli, Massimo; Weber, Dieter G; Ruppé, Etienne; Bassetti, Matteo; Wright, Brian J; Ansaloni, Luca; Catena, Fausto; Coccolini, Federico; Abu-Zidan, Fikri M; Coimbra, Raul; Moore, Ernest E; Moore, Frederick A; Maier, Ronald V; De Waele, Jan J; Kirkpatrick, Andrew W; Griffiths, Ewen A; Eckmann, Christian; Brink, Adrian J; Mazuski, John E; May, Addison K; Sawyer, Rob G; Mertz, Dominik; Montravers, Philippe; Kumar, Anand; Roberts, Jason A; Vincent, Jean-Louis; Watkins, Richard R; Lowman, Warren; Spellberg, Brad; Abbott, Iain J; Adesunkanmi, Abdulrashid Kayode; Al-Dahir, Sara; Al-Hasan, Majdi N; Agresta, Ferdinando; Althani, Asma A; Ansari, Shamshul; Ansumana, Rashid; Augustin, Goran; Bala, Miklosh; Balogh, Zsolt J; Baraket, Oussama; Bhangu, Aneel; Beltrán, Marcelo A; Bernhard, Michael; Biffl, Walter L; Boermeester, Marja A; Brecher, Stephen M; Cherry-Bukowiec, Jill R; Buyne, Otmar R; Cainzos, Miguel A; Cairns, Kelly A; Camacho-Ortiz, Adrian; Chandy, Sujith J; Che Jusoh, Asri; Chichom-Mefire, Alain; Colijn, Caroline; Corcione, Francesco; Cui, Yunfeng; Curcio, Daniel; Delibegovic, Samir; Demetrashvili, Zaza; De Simone, Belinda; Dhingra, Sameer; Diaz, José J; Di Carlo, Isidoro; Dillip, Angel; Di Saverio, Salomone; Doyle, Michael P; Dorj, Gereltuya; Dogjani, Agron; Dupont, Hervé; Eachempati, Soumitra R; Enani, Mushira Abdulaziz; Egiev, Valery N; Elmangory, Mutasim M; Ferrada, Paula; Fitchett, Joseph R; Fraga, Gustavo P; Guessennd, Nathalie; Giamarellou, Helen; Ghnnam, Wagih; Gkiokas, George; Goldberg, Staphanie R; Gomes, Carlos Augusto; Gomi, Harumi; Guzmán-Blanco, Manuel; Haque, Mainul; Hansen, Sonja; Hecker, Andreas; Heizmann, Wolfgang R; Herzog, Torsten; Hodonou, Adrien Montcho; Hong, Suk-Kyung; Kafka-Ritsch, Reinhold; Kaplan, Lewis J; Kapoor, Garima; Karamarkovic, Aleksandar; Kees, Martin G; Kenig, Jakub; Kiguba, Ronald; Kim, Peter K; Kluger, Yoram; Khokha, Vladimir; Koike, Kaoru; Kok, Kenneth Y Y; Kong, Victory; Knox, Matthew C; Inaba, Kenji; Isik, Arda; Iskandar, Katia; Ivatury, Rao R; Labbate, Maurizio; Labricciosa, Francesco M; Laterre, Pierre-François; Latifi, Rifat; Lee, Jae Gil; Lee, Young Ran; Leone, Marc; Leppaniemi, Ari; Li, Yousheng; Liang, Stephen Y; Loho, Tonny; Maegele, Marc; Malama, Sydney; Marei, Hany E; Martin-Loeches, Ignacio; Marwah, Sanjay; Massele, Amos; McFarlane, Michael; Melo, Renato Bessa; Negoi, Ionut; Nicolau, David P; Nord, Carl Erik; Ofori-Asenso, Richard; Omari, AbdelKarim H; Ordonez, Carlos A; Ouadii, Mouaqit; Pereira Júnior, Gerson Alves; Piazza, Diego; Pupelis, Guntars; Rawson, Timothy Miles; Rems, Miran; Rizoli, Sandro; Rocha, Claudio; Sakakushev, Boris; Sanchez-Garcia, Miguel; Sato, Norio; Segovia Lohse, Helmut A; Sganga, Gabriele; Siribumrungwong, Boonying; Shelat, Vishal G; Soreide, Kjetil; Soto, Rodolfo; Talving, Peep; Tilsed, Jonathan V; Timsit, Jean-Francois; Trueba, Gabriel; Trung, Ngo Tat; Ulrych, Jan; van Goor, Harry; Vereczkei, Andras; Vohra, Ravinder S; Wani, Imtiaz; Uhl, Waldemar; Xiao, Yonghong; Yuan, Kuo-Ching; Zachariah, Sanoop K; Zahar, Jean-Ralph; Zakrison, Tanya L; Corcione, Antonio; Melotti, Rita M; Viscoli, Claudio; Viale, Perluigi

2016-01-01

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

Evaluation of the Clinical Impact of the Biofire Filmarray® Rapid Multiplex PCR Assay in Blood Culture Identification Combined with Antimicrobial Stewardship Intervention

PubMed Central

Andujar-Vazquez, Gabriela M; Gardiner, Bradley; Magro, Francis; Beaulac, Kirthana R; Doron, Shira; Snydman, David R

2017-01-01

Abstract Background Bloodstream infections are a major cause of morbidity and mortality worldwide, with favorable clinical outcomes associated with early optimal antibiotic selection. Rapid diagnostics have become a key part in achieving this. Biofire Filmarray® was introduced at our institution for rapid blood culture (BC) identification, coupled with antimicrobial stewardship (AS) interventions. We aimed to assess the impact of this test on time to adequate antimicrobial therapy in a setting with pre-existing effective AS interventions. Methods An observational retrospective chart review, pre and post study was performed. We reviewed adult positive BC before and after implementation of Biofire. Outcomes were: (1) time from BC result reported to health care provider to start of adequate antimicrobial therapy,(2) time to stopping antimicrobial therapy in BC thought to be contaminants, (3) time to any change in antimicrobial therapy and (4) a composite outcome of outcomes 1 and 2. A univariate Cox proportional hazards model was performed. Results 326 positive BC were analyzed, 173 before and 153 after Biofire implementation. At the time of healthcare provider notification, 77 were not on adequate antimicrobials, with median time to adequate therapy of 6.98 hours. (IQR 3.93–23.96) before and 6.1 hours. (IQR 1.84–20.95) after implementation, P = 0.48. There were 75 BC classified as contaminants and median time to stopping antimicrobials was 48.28 (IQR 18.56–89.36) vs. 45.25 hours. (IQR 15.12–100.60), P = 0.61. Time to any change in any antimicrobial therapy was similar with a median of 13.05 (IQR 4.00–36.77) vs. 10.90 hours. (IQR 2.97–31.10), P = 0.87. Analysis of the composite outcome revealed a median of 23.95 (6.29–58.50) vs. 14.82 (IQR 4.07–44.79) hours. (Hazard ratio 1.33, 95% confidence interval 0.96–1.84, P = 0.09). Conclusion Implementation of the Biofire Filmarray® did not have a statistically significant effect on our composite outcome of time to adequate therapy and time to discontinuation in the case of contaminants. Our findings suggests that when added to other effective AS surveillance and interventions, the magnitude of the clinical impact of rapid PCR diagnostics for BC identification is minimal. Disclosures D. R. Snydman, Merck: Scientific Advisor, Consulting fee; Shire: Scientific Advisor, Consulting fee

Bacteriocin-Antimicrobial Synergy: A Medical and Food Perspective

PubMed Central

Mathur, Harsh; Field, Des; Rea, Mary C.; Cotter, Paul D.; Hill, Colin; Ross, R. Paul

2017-01-01

The continuing emergence of multi-drug resistant pathogens has sparked an interest in seeking alternative therapeutic options. Antimicrobial combinatorial therapy is one such avenue. A number of studies have been conducted, involving combinations of bacteriocins with other antimicrobials, to circumvent the development of antimicrobial resistance and/or increase antimicrobial potency. Such bacteriocin-antimicrobial combinations could have tremendous value, in terms of reducing the likelihood of resistance development due to the involvement of two distinct mechanisms of antimicrobial action. Furthermore, antimicrobial synergistic interactions may also have potential financial implications in terms of decreasing the costs of treatment by reducing the concentration of an expensive antimicrobial and utilizing it in combination with an inexpensive one. In addition, combinatorial therapies with bacteriocins can broaden antimicrobial spectra and/or result in a reduction in the concentration of an antibiotic required for effective treatments to the extent that potentially toxic or adverse side effects can be reduced or eliminated. Here, we review studies in which bacteriocins were found to be effective in combination with other antimicrobials, with a view to targeting clinical and/or food-borne pathogens. Furthermore, we discuss some of the bottlenecks which are currently hindering the development of bacteriocins as viable therapeutic options, as well as addressing the need to exercise caution when attempting to predict clinical outcomes of bacteriocin-antimicrobial combinations. PMID:28706513

Impact of an antimicrobial stewardship intervention on appropriateness of prescribing for community-acquired pneumonia in an Australian regional hospital.

PubMed

Bond, Stuart E; Boutlis, Craig S; Yeo, Wilfred W; Miyakis, Spiros

2017-05-01

Community-acquired pneumonia (CAP) is the second commonest indication for antibiotic use in Australian hospitals and is therefore a frequent target for antimicrobial stewardship. A single-centre prospective study was conducted in a regional referral hospital comparing management of adult patients with CAP before and after an educational intervention. We demonstrated a reduction in duration of therapy and reduced inappropriate use of ceftriaxone-based regimens for non-severe CAP. © 2017 Royal Australasian College of Physicians.

Antimicrobial usage and risk of retreatment for mild to moderate clinical mastitis cases on dairy farms following on-farm bacterial culture and selective therapy.

PubMed

McDougall, S; Niethammer, J; Graham, E M

2018-03-01

To assess antimicrobial usage for treatment of mild to moderate clinical mastitis, and risk of retreatment, following implementation of an on-farm bacterial culture system and selective therapy based on culture results, and to assess compliance with treatment decision tree protocols and the level of agreement between results from on-farm culture and laboratory-based microbiology methods. Herdowners from seven dairy herds were asked to collect milk samples from cases of mild to moderate clinical mastitis between July 2015 and May 2016. All samples were cultured on-farm using a commercially available selective media and were also submitted for laboratory-based culture. Within sequential pairs of cows with mastitis, half were assigned to be treated without regard to culture results (Blanket group), and half were treated based on the on-farm culture results (Selective group) according to decision tree diagrams provided to the farmers. Culture results, treatments, and retreatments for clinical mastitis were recorded. The sum of the daily doses of antimicrobials used per cow, the number of retreatments and interval to first retreatment were compared between treatment groups. The geometric mean sum of daily doses for quarters assigned to the Selective (1.72 (95% CI=1.55-1.90)) group was lower than for the Blanket (2.38 (95% CI=2.17-2.60)) group (p=0.005). The percentage of cows retreated for clinical mastitis did not differ between the Selective (21.7 (95% CI=10.5-25.9)%) and Blanket (26.1 (95% CI=20.9-31.3)%) groups (p=0.13), and there was no difference between groups in the hazard that cows would be retreated within 60 days of enrolment (hazard ratio=0.82 (95% CI=0.39-1.69); p=0.59). Compliance with the treatment protocols was higher amongst quarters assigned to the Selective (199/233; 85.4%) compared with the Blanket (171/249; 68.7%) group (p<0.001), and varied between farms from 64-94%. The overall agreement between results from on-farm and laboratory culture was 188/331 (56.9%; kappa=0.31; p<0.001), but varied between farms from 44.7-88.2% (p<0.001). Use of on-farm culture with selective antimicrobial therapy resulted in approximately 25% lower antimicrobial usage, but was not associated with an increase in the proportion of cows retreated for clinical mastitis. This study has demonstrated that on-farm culture and selective therapy based on culture results can be implemented on-farm. However, farms varied in their implementation of both the treatment protocols and microbiology procedures. Where such systems are to be used on-farm, specific training and on-going monitoring is required.

Impact of real-time notification of Clostridium difficile test results and early initiation of effective antimicrobial therapy.

PubMed

Polen, Christian B; Judd, William R; Ratliff, Patrick D; King, Gregory S

2018-05-01

Clostridium difficile is a prominent nosocomial pathogen and is the most common causative organism of health care-associated diarrhea. To our knowledge, no studies have investigated the impact of real-time notification of culture results with rapid antimicrobial stewardship program (ASP) intervention in the setting of C difficile infection (CDI). The purpose of this study was to assess the impact of real-time notification of detection of toxigenic C difficile by DNA amplification results in patients with confirmed CDI. This is a single-center, retrospective cohort study at a 433-bed tertiary medical center in central Kentucky. The study consisted of 2 arms: patients treated for CDI prior to implementation of real-time provider notification and patients postimplementation. The primary outcome was time to initiation of effective antimicrobial therapy. The median time to initiation of effective antimicrobial therapy decreased from 5.75 hours in the preimplementation cohort to 2.05 hours in the postimplementation cohort (P = .001). ASP intervention also resulted in a shorter time from detection of CDI to order entry of effective antimicrobial therapy in the patient's electronic medical record (3.0 vs 0.6 hours; P = .001). The implementation of a real-time notification system to alert a pharmacist-led ASP of toxigenic CDI resulted in statistically significant shorter times to order entry and subsequent initiation of effective antimicrobial therapy and contact precautions. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Innovative strategies to overcome biofilm resistance.

PubMed

Taraszkiewicz, Aleksandra; Fila, Grzegorz; Grinholc, Mariusz; Nakonieczna, Joanna

2013-01-01

We review the recent literature concerning the efficiency of antimicrobial photodynamic inactivation toward various microbial species in planktonic and biofilm cultures. The review is mainly focused on biofilm-growing microrganisms because this form of growth poses a threat to chronically infected or immunocompromised patients and is difficult to eradicate from medical devices. We discuss the biofilm formation process and mechanisms of its increased resistance to various antimicrobials. We present, based on data in the literature, strategies for overcoming the problem of biofilm resistance. Factors that have potential for use in increasing the efficiency of the killing of biofilm-forming bacteria include plant extracts, enzymes that disturb the biofilm structure, and other nonenzymatic molecules. We propose combining antimicrobial photodynamic therapy with various antimicrobial and antibiofilm approaches to obtain a synergistic effect to permit efficient microbial growth control at low photosensitizer doses.

Antimicrobial Peptides in 2014

PubMed Central

Wang, Guangshun; Mishra, Biswajit; Lau, Kyle; Lushnikova, Tamara; Golla, Radha; Wang, Xiuqing

2015-01-01

This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms. PMID:25806720

When sepsis persists: a review of MRSA bacteraemia salvage therapy.

PubMed

Kullar, Ravina; Sakoulas, George; Deresinski, Stan; van Hal, Sebastiaan J

2016-03-01

MRSA bacteraemia (MRSAB), including infective endocarditis, carries a high mortality rate, with up to 50% of patients failing initial therapy with vancomycin and requiring salvage therapy. Persistent MRSAB can be difficult to successfully eliminate, especially when source control is not possible due to an irremovable focus or the bacteraemia still persists despite surgical intervention. Although vancomycin and daptomycin are the only two antibiotics approved by the US FDA for the treatment of patients with MRSAB as monotherapy, the employment of novel strategies is required to effectively treat patients with persistent MRSAB and these may frequently involve combination drug therapy. Treatment strategies that are reviewed in this manuscript include vancomycin combined with a β-lactam, daptomycin-based therapy, ceftaroline-based therapy, linezolid-based therapy, quinupristin/dalfopristin, telavancin, trimethoprim/sulfamethoxazole-based therapy and fosfomycin-based therapy. We recommend that combination antibiotic therapy be considered for use in MRSAB salvage treatment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cardiac Electrophysiology Laboratories: A Potential Target for Antimicrobial Stewardship and Quality Improvement?

PubMed

Branch-Elliman, Westyn; Stanislawski, Maggie; Strymish, Judith; Barón, Anna E; Gupta, Kalpana; Varosy, Paul D; Gold, Howard S; Ho, P Michael

2016-09-01

BACKGROUND Infections following cardiovascular implantable electronic device (CIED) procedures, including pacemaker and implantable cardioverter-defibrillators, are devastating and costly. Preimplantation prophylactic antimicrobials are effective for reducing postprocedural infections. However, routine postprocedural antimicrobials are not associated with improved outcomes, and they may be harmful. Thus, we sought to characterize antimicrobial use patterns following CIED procedures. DESIGN All patients who underwent CIED procedures from October 1, 2007 to September 30, 2013 and had procedural information entered into the VA Clinical Assessment Reporting and Tracking (CART) software program were included in this study. All antibiotic prescriptions lasting more than 24 hours following device implantation or revision were identified using pharmacy databases, and postprocedural antibiotic use lasting more than 24 hours was characterized. RESULTS In total, 3,712 CIED procedures were performed at 34 VA facilities on 3,570 patients with a mean age of 71.7 years (standard deviation [SD], 11.1 years), 98.4% of whom were male. Postprocedural antibiotics >24 hours were prescribed following 1,579 of 3,712 CIED procedures (42.5%). The median duration of therapy was 5 days (interquartile range [IQR], 3-7 days). The most commonly prescribed antibiotic was cephalexin (1,152 of 1,579; 72.9%), followed by doxycycline (118 of 1,579; 7.47%) and ciprofloxacin (93 of 1,579; 5.9%). Vancomycin was used in 73 of 1,579 prescriptions (4.62%). Among the highest quartile of procedural volume, prescribing practices varied considerably, ranging from 3.2% to 77.6%. CONCLUSIONS Nearly 1 in 2 patients received prolonged postprocedural antimicrobial therapy following CIED procedures, and the rate of postprocedural antimicrobial therapy use varied considerably by facility. Given the lack of demonstrated benefit of routine prolonged antimicrobial therapy following CIED procedures, antimicrobial use following cardiac device interventions may be a potential target for quality improvement programs and antimicrobial stewardship. Infect Control Hosp Epidemiol 2016;37:1005-1011.

Antimicrobial therapy of selected diseases in turkeys, laying hens, and minor poultry species in Canada

PubMed Central

Agunos, Agnes; Carson, Carolee; Léger, Dave

2013-01-01

This paper identifies common poultry diseases requiring antimicrobial therapy, antimicrobials deemed efficacious to treat these diseases, and antimicrobial resistance (AMR) in these commodity-pathogen combinations, and describes current residue issues and minor use minor species (MUMS) guidelines. Veterinarians with turkey/layer expertise and diagnosticians were surveyed to determine the bacterial and protozoal diseases diagnosed in the last 5 years. Avian pathogenic Escherichia coli, Staphylococcus aureus, and Ornithobacterium rhinotracheale were the 3 most frequently diagnosed pathogens of turkeys. In layers, E. coli-peritonitis, and Clostridium perfringens/Eimeria spp. infections were the most common diagnoses. A literature review identified 32 antimicrobials as efficacious and/or recommended for treating these diseases. Surveillance and monitoring indicate the presence of enteric resistant organisms from some of these avian species (including resistance to antimicrobials of very high importance to human medicine). This paper highlights the need for surveillance of pathogen frequency, antimicrobial use (AMU), and AMR particularly in turkeys. PMID:24179239

Phage Therapy: Beyond Antibacterial Action.

PubMed

Górski, Andrzej; Jończyk-Matysiak, Ewa; Międzybrodzki, Ryszard; Weber-Dąbrowska, Beata; Łusiak-Szelachowska, Marzanna; Bagińska, Natalia; Borysowski, Jan; Łobocka, Małgorzata B; Węgrzyn, Alicja; Węgrzyn, Grzegorz

2018-01-01

Until recently, phages were considered as mere "bacteria eaters" with potential for use in combating antimicrobial resistance. The real value of phage therapy assessed according to the standards of evidence-based medicine awaits confirmation by clinical trials. However, the progress in research on phage biology has shed more light on the significance of phages. Accumulating data indicate that phages may also interact with eukaryotic cells. How such interactions could be translated into advances in medicine (especially novel means of therapy) is discussed herein.

Topical Antimicrobials for Burn Infections – An Update

PubMed Central

Sevgi, Mert; Toklu, Ani; Vecchio, Daniela; Hamblin, Michael R

2014-01-01

The relentless rise in antibiotic resistance among pathogenic bacteria and fungi, coupled with the high susceptibility of burn wounds to infection, and the difficulty of systemically administered antibiotics to reach damaged tissue, taken together have made the development of novel topical antimicrobials for burn infections a fertile area of innovation for researchers and companies. We previously covered the existing patent literature in this area in 2010, but the notable progress made since then, has highlighted the need for an update to bring the reader up to date on recent developments. New patents in the areas of topically applied antibiotics and agents that can potentiate the action of existing antibiotics may extend their useful lifetime. Developments have also been made in biofilm-disrupting agents. Antimicrobial peptides are nature’s way for many life forms to defend themselves against attack by pathogens. Silver has long been known to be a highly active antimicrobial but new inorganic metal derivatives based on bismuth, copper and gallium have emerged. Halogens such as chlorine and iodine can be delivered by novel technologies. A variety of topically applied antimicrobials include chitosan preparations, usnic acid, ceragenins and XF porphyrins. Natural product derived antimicrobials such as tannins and essential oils have also been studied. Novel techniques to deliver reactive oxygen species and nitric oxide in situ have been developed. Light-mediated techniques include photodynamic therapy, ultraviolet irradiation, blue light, low-level laser therapy and titania photocatalysis. Passive immunotherapy employs antibodies against pathogens and their virulence factors. Finally an interesting new area uses therapeutic microorganisms such as phages, probiotic bacteria and protozoa to combat infections. PMID:24215506

A retrospective analysis of antimicrobial resistance in bacterial pathogens in an equine hospital (2012-2015).

PubMed

van Spijk, J N; Schmitt, S; Fürst, A E; Schoster, A

2016-06-01

Antimicrobial resistance has become an important concern in veterinary medicine. The aim of this study was to describe the rate of antimicrobial resistance in common equine pathogens and to determine the occurrence of multidrug-resistant isolates. A retrospective analysis of all susceptibility testing results from bacterial pathogens cultured from horses at the University of Zurich Equine Hospital (2012-2015) was performed. Strains exhibiting resistance to 3 or more antimicrobial categories were defined as multidrug-resistant. Susceptibility results from 303 bacterial pathogens were analyzed, most commonly Escherichia coli (60/303, 20%) and Staphylococcus aureus (40/303, 13%). High rates of acquired resistance against commonly used antimicrobials were found in most of the frequently isolated equine pathogens. The highest rate of multidrug resistance was found in isolates of Acinetobacter baumannii (23/24, 96%), followed by Enterobacter cloacae complex (24/28, 86%) and Escherichia coli (48/60, 80%). Overall, 60% of Escherichia coli isolates were phenotypically ESBL-producing and 68% of Staphylococcus spp. were phenotypically methicillin-resistant. High rates of acquired antimicrobial resistance towards commonly used antibiotics are concerning and underline the importance of individual bacteriological and antimicrobial susceptibility testing to guide antimicrobial therapy. Minimizing and optimizing antimicrobial therapy in horses is needed.

High-Throughput Intracellular Antimicrobial Susceptibility Testing of Legionella pneumophila.

PubMed

Chiaraviglio, Lucius; Kirby, James E

2015-12-01

Legionella pneumophila is a Gram-negative opportunistic human pathogen that causes a severe pneumonia known as Legionnaires' disease. Notably, in the human host, the organism is believed to replicate solely within an intracellular compartment, predominantly within pulmonary macrophages. Consequently, successful therapy is predicated on antimicrobials penetrating into this intracellular growth niche. However, standard antimicrobial susceptibility testing methods test solely for extracellular growth inhibition. Here, we make use of a high-throughput assay to characterize intracellular growth inhibition activity of known antimicrobials. For select antimicrobials, high-resolution dose-response analysis was then performed to characterize and compare activity levels in both macrophage infection and axenic growth assays. Results support the superiority of several classes of nonpolar antimicrobials in abrogating intracellular growth. Importantly, our assay results show excellent correlations with prior clinical observations of antimicrobial efficacy. Furthermore, we also show the applicability of high-throughput automation to two- and three-dimensional synergy testing. High-resolution isocontour isobolograms provide in vitro support for specific combination antimicrobial therapy. Taken together, findings suggest that high-throughput screening technology may be successfully applied to identify and characterize antimicrobials that target bacterial pathogens that make use of an intracellular growth niche. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

High-Throughput Intracellular Antimicrobial Susceptibility Testing of Legionella pneumophila

PubMed Central

Chiaraviglio, Lucius

2015-01-01

Legionella pneumophila is a Gram-negative opportunistic human pathogen that causes a severe pneumonia known as Legionnaires' disease. Notably, in the human host, the organism is believed to replicate solely within an intracellular compartment, predominantly within pulmonary macrophages. Consequently, successful therapy is predicated on antimicrobials penetrating into this intracellular growth niche. However, standard antimicrobial susceptibility testing methods test solely for extracellular growth inhibition. Here, we make use of a high-throughput assay to characterize intracellular growth inhibition activity of known antimicrobials. For select antimicrobials, high-resolution dose-response analysis was then performed to characterize and compare activity levels in both macrophage infection and axenic growth assays. Results support the superiority of several classes of nonpolar antimicrobials in abrogating intracellular growth. Importantly, our assay results show excellent correlations with prior clinical observations of antimicrobial efficacy. Furthermore, we also show the applicability of high-throughput automation to two- and three-dimensional synergy testing. High-resolution isocontour isobolograms provide in vitro support for specific combination antimicrobial therapy. Taken together, findings suggest that high-throughput screening technology may be successfully applied to identify and characterize antimicrobials that target bacterial pathogens that make use of an intracellular growth niche. PMID:26392509

Acyldepsipeptide antibiotics as a potential therapeutic agent against Clostridium difficile recurrent infections.

PubMed

Gil, Fernando; Paredes-Sabja, Daniel

2016-09-01

Alternative antimicrobial therapies based on acyldepsipeptides may hold promising results, based on the fact that they have shown to efficiently eradicate persister cells, stationary cells and cell in biofilm structures of several pathogenic bacteria from the infected host. Clostridium difficile infection is considered the result of extensive hospital use of expanded-spectrum antibiotics, which cause dysbiosis of the intestinal microbiota, enhancing susceptibility to infection and persistence. Considering the urgent need for the development of novel and efficient antimicrobial strategies against C. difficile, we review the potential application to treat C. difficile infections of acyldepsipeptides family of antibiotics, its mechanism of action and current developmental stages.

Quantification of antimicrobial consumption in adult cattle on dairy herds in Flanders, Belgium, and associations with udder health, milk quality, and production performance.

PubMed

Stevens, M; Piepers, S; Supré, K; Dewulf, J; De Vliegher, S

2016-03-01

The main objective of this study was to quantify the (compound-specific) antimicrobial consumption (AMC) in adult cattle in a convenience sample of Flemish dairy herds. Antimicrobial consumption data were obtained between 2012 and 2013 by "garbage can audits" and expressed as antimicrobial treatment incidence (ATI), with the unit of the ATI being the number of defined daily doses animal (DDDA) used per 1,000 cow-days. Herds were stratified by DDDA into low-, medium-, and high-consuming herds to study the AMC per route of administration, and associations with parameters reflecting udder health, milk quality, and production performances were examined. The average ATI in adult dairy cattle for all compounds was 20.78 DDDA (per 1,000 cow-days). Large variation existed between herds (ranging from 8.68 to 41.62 DDDA). Fourth-generation cephalosporins were used most (4.99 DDDA), followed by penicillins (3.70 DDDA) and third-generation cephalosporins (2.95 DDDA). The average ATI of the critically important antimicrobials for human health (i.e., third- and fourth-generation cephalosporins and fluoroquinolones according to the World Organisation for Animal Health classification) was somewhat lower than the average ATI of the other antimicrobials (8.59 and 12.18 DDDA, respectively). The average ATI for intramammary treatment of (sub)clinical mastitis, for dry-cow therapy, and for systemically administered antimicrobials was 6.30, 6.89, and 7.44 DDDA, respectively. In low-consuming herds, most antimicrobials were being used for dry-cow therapy, whereas in high-consuming herds, most antimicrobials were being used as injectable or intramammary mastitis therapy. The incidence rate of treated mastitis was positively associated with ATI. Herds that applied blanket dry-cow therapy tended to have a higher ATI than herds in which cows were selectively dried off with long-acting antimicrobials. The ATI decreased with an increasing prevalence of primiparous cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Risk factors for Pseudomonas aeruginosa infections consequences of inappropriate initial antimicrobial therapy: a systematic literature review meta-analysis.

PubMed

Merchant, Sanjay; Proudfoot, Emma M; Quadri, Hafsa N; McElroy, Heather J; Wright, William R; Gupta, Ankur; Sarpong, Eric M

2018-02-15

Treating infections of Gram-negative pathogens, in particular Pseudomonas aeruginosa, is a challenge for clinicians in the Asia-Pacific region due to inherent and acquired resistance to antimicrobials. This systematic review and meta-analysis provides updated information of the risk factors for P. aeruginosa infections in Asia-Pacific, and consequences (e.g., mortality, costs) of initial inappropriate antimicrobial therapy (IIAT). EMBASE and MEDLINE databases were searched for Asia-Pacific studies reporting the consequences of IIAT versus initial appropriate antimicrobial therapy (IAAT) in Gram-negative infections, and risk factors for serious P. aeruginosa infections. A meta-analysis of unadjusted mortality was performed using random-effects model. Twenty-two studies reporting mortality and 13 reporting risk factors were identified. The meta-analysis demonstrated that mortality was significantly lower in patients receiving IAAT versus IIAT, with 67% reduction observed for 28- or 30-day all-cause mortality (OR 0.33; 95% CI 0.20, 0.55; P <0.001). Risk factors for serious P. aeruginosa infection include previous exposure to antimicrobials, mechanical ventilation, and previous hospitalization. The high rates of antimicrobial resistance in Asia-Pacific, as well as increased mortality associated with IIAT and the presence of risk factors for serious infection, highlight the importance of access to newer and appropriate antimicrobials. Copyright © 2018. Published by Elsevier Ltd.

Editorial--Avoiding Unethical Helicobacter pylori Clinical Trials: Susceptibility-Based Studies and Probiotics as Adjuvants.

PubMed

Graham, David Y

2015-10-01

As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g., in a population with known clarithromycin resistance) is unethical. As susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance >0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies, and studies of adjuvants and probiotics. However, the journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors, we provide examples and suggestions regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics. © 2015 John Wiley & Sons Ltd.

Editorial - Avoiding unethical Helicobacter pylori clinical trials: Susceptibility-based studies and probiotics as adjuvants

PubMed Central

Graham, David Y.

2016-01-01

As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g. in a population with known clarithromycin resistance) is unethical. Since susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance greater than 0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies and of adjuvants and probiotics. However, the Journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors we provide examples and suggestion regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics. PMID:26123529

Antimicrobial Activity of Calcium Hydroxide in Endodontics: A Review

PubMed Central

Shalavi, S; Yazdizadeh, M

2012-01-01

The purpose of endodontic therapy is to preserve the patient's natural teeth without compromising the patient's local or systemic health. Calcium hydroxide has been included in several materials and antimicrobial formulations that are used in several treatment modalities in endodontics, such as inter-appointment intracanal medicaments. The purpose of this article was to review the antimicrobial properties of calcium hydroxide in endodontics. Calcium hydroxide has a high pH (approximately 12.5-12.8) and is classified chemically as a strong base. The lethal effects of calcium hydroxide on bacterial cells are probably due to protein denaturation and damage to DNA and cytoplasmic membranes. Calcium hydroxide has a wide range of antimicrobial activity against common endodontic pathogens but is less effective against Enterococcus faecalis and Candida albicans. Calcium hydroxide is also a valuable anti-endotoxin agent. However, its effect on microbial biofilms is controversial. PMID:23323217

Technical report—Diagnosis and management of an initial UTI in febrile infants and young children.

PubMed

Finnell, S Maria E; Carroll, Aaron E; Downs, Stephen M

2011-09-01

The diagnosis and management of urinary tract infections (UTIs) in young children are clinically challenging. This report was developed to inform the revised, evidence-based, clinical guideline regarding the diagnosis and management of initial UTIs in febrile infants and young children, 2 to 24 months of age, from the American Academy of Pediatrics Subcommittee on Urinary Tract Infection. The conceptual model presented in the 1999 technical report was updated after a comprehensive review of published literature. Studies with potentially new information or with evidence that reinforced the 1999 technical report were retained. Meta-analyses on the effectiveness of antimicrobial prophylaxis to prevent recurrent UTI were performed. Review of recent literature revealed new evidence in the following areas. Certain clinical findings and new urinalysis methods can help clinicians identify febrile children at very low risk of UTI. Oral antimicrobial therapy is as effective as parenteral therapy in treating UTI. Data from published, randomized controlled trials do not support antimicrobial prophylaxis to prevent febrile UTI when vesicoureteral reflux is found through voiding cystourethrography. Ultrasonography of the urinary tract after the first UTI has poor sensitivity. Early antimicrobial treatment may decrease the risk of renal damage from UTI. Recent literature agrees with most of the evidence presented in the 1999 technical report, but meta-analyses of data from recent, randomized controlled trials do not support antimicrobial prophylaxis to prevent febrile UTI. This finding argues against voiding cystourethrography after the first UTI.

Malignant external otitis: long-term (months) antimicrobial therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strauss, M.; Aber, R.C.; Conner, G.H.

1982-04-01

Since Chandler's initial report in 1968 on malignant external otitis (MEO), this entity has been recognized in its earlier stages with increasing frequency. As a result of this, the availability of new antimicrobial agents, and the judicious use of surgery, there has been an improvement in the results of therapy. There remains, however, a subgroup of patients who continue to experience a significant mortality from this infection. A review and selected discussion of our experience with MEO from 1976 to 1979 is presented. Six patients have been diagnosed and successfully treated for MEO. They presented with problems ranging from severemore » otalgia to multiple cranial neuropathy. For the most part, therapy consisted of the now standard aminoglycoside and carbenicillin combination. Two of the patients were in the high mortality risk group. One of these patients developed an osteomyelitis which extended across the skull base resulting in bilateral cranial neuropathies. His therapy included surgery as well as long-term (months) outpatient treatment with tobramycin and carbenicillin with an excellent result. The second patient was treated similarly. The efficacy of this approach is discussed as well as the usefulness of radionuclide bone scanning in assessing the course and therapy of patients with MEO.« less

Extended biofilm susceptibility assay for Staphylococcus aureus bovine mastitis isolates: evidence for association between genetic makeup and biofilm susceptibility.

PubMed

Melchior, M B; van Osch, M H J; Lam, T J G M; Vernooij, J C M; Gaastra, W; Fink-Gremmels, J

2011-12-01

Staphylococcus aureus is one of the most prevalent causes of bovine mastitis. The antimicrobial treatment of this disease is currently based on antimicrobial susceptibility tests according to Clinical and Laboratory Standards Institute standards. However, various authors have shown a discrepancy between the results of this standard susceptibility test and the actual cure rate of the applied antimicrobial treatment. Increasing evidence suggests that in vivo biofilm formation by Staph. aureus, which is not assessed in the antimicrobial susceptibility tests, is associated with this problem, resulting in disappointing cure rates, especially for infections of longer duration. Previous data obtained with a limited number of strains showed that the extended biofilm antimicrobial susceptibility (EBS) assay reveals differences between strains, which cannot be derived from a standard susceptibility test or from a 24-h biofilm susceptibility test. The objective of this study was to test a collection of Staph. aureus bovine mastitis strains in the EBS assay and to model the effect of antimicrobial exposure, duration of antimicrobial exposure, and genotype profile of the strains on antimicrobial susceptibility. With the results from a previous study with the same collection of strains, the effect of genotype represented by accessory gene regulator gene (agr-type), the presence of insertional sequence 257 (IS257), intercellular adhesion (ica), and the β-lactamase (blaZ) gene were entered as explanatory factors in a logistic regression model. The agr locus of Staph. aureus controls the expression of most of the virulence factors, represses the transcription of several cell wall-associated proteins, and activates several exoproteins during the post-exponential phase. The IS257 gene has been related to biofilm formation in vitro and was found earlier in 50% of the agr-type 2 strains. The ica gene cluster encodes for the production of an extracellular polysaccharide adhesin, termed polysaccharide intercellular adhesin, which appears to have an important role in pathogenic Staph. aureus infections. The blaZ gene encodes the presence of the penicillin resistance in the strain. The EBS assay together with the logistic regression model revealed that the duration of therapy is the most important factor of therapy outcome in this in vitro model. Furthermore, the effect of genotypic differences seems to be more important for therapy outcome than the antimicrobial used in this model. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Bacterial Cytological Profiling (BCP) as a Rapid and Accurate Antimicrobial Susceptibility Testing Method for Staphylococcus aureus.

PubMed

Quach, D T; Sakoulas, G; Nizet, V; Pogliano, J; Pogliano, K

2016-02-01

Successful treatment of bacterial infections requires the timely administration of appropriate antimicrobial therapy. The failure to initiate the correct therapy in a timely fashion results in poor clinical outcomes, longer hospital stays, and higher medical costs. Current approaches to antibiotic susceptibility testing of cultured pathogens have key limitations ranging from long run times to dependence on prior knowledge of genetic mechanisms of resistance. We have developed a rapid antimicrobial susceptibility assay for Staphylococcus aureus based on bacterial cytological profiling (BCP), which uses quantitative fluorescence microscopy to measure antibiotic induced changes in cellular architecture. BCP discriminated between methicillin-susceptible (MSSA) and -resistant (MRSA) clinical isolates of S. aureus (n = 71) within 1-2 h with 100% accuracy. Similarly, BCP correctly distinguished daptomycin susceptible (DS) from daptomycin non-susceptible (DNS) S. aureus strains (n = 20) within 30 min. Among MRSA isolates, BCP further identified two classes of strains that differ in their susceptibility to specific combinations of beta-lactam antibiotics. BCP provides a rapid and flexible alternative to gene-based susceptibility testing methods for S. aureus, and should be readily adaptable to different antibiotics and bacterial species as new mechanisms of resistance or multidrug-resistant pathogens evolve and appear in mainstream clinical practice.

Natural Antimicrobials and Oral Microorganisms: A Systematic Review on Herbal Interventions for the Eradication of Multispecies Oral Biofilms

PubMed Central

Karygianni, Lamprini; Al-Ahmad, Ali; Argyropoulou, Aikaterini; Hellwig, Elmar; Anderson, Annette C.; Skaltsounis, Alexios L.

2016-01-01

Oral diseases such as caries and periodontitis are mainly caused by microbial biofilms. Antibiotic therapy has reached its limits with regard to antimicrobial resistance, and new therapeutic measures utilizing natural phytochemicals are currently a focus of research. Hence, this systematic review provides a critical presentation of the antimicrobial effects of various medicinal herbs against in vitro, ex vivo, and in situ formed multispecies oral biofilms. Searches were performed in three English databases (PubMed, EMBASE, CAMbase) and the electronic archives of five German journals from the times of their establishment until October 10th, 2014, with the search terms “(plant extracts OR herbal extracts OR plant OR herb) AND (oral biofilm OR dental biofilm OR dental plaque OR oral disease OR dental disease).” The pooled data were assessed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Initially, 1848 articles were identified, out of which 585 full-text articles were screened, 149 articles were reevaluated for eligibility and finally, 14 articles met all inclusion criteria. The data of 14 reports disclosed enhanced antiadhesive and antibiofilm activity by the plant extracts obtained from Vitis vinifera, Pinus spp., Coffea canephora, Camellia sinensis, Vaccinium macrocarpon, Galla chinensis, Caesalpinia ferrea Martius, Psidium cattleianum, representative Brazilian plants and manuka honey. Overall, a positive correlation was revealed between herb-based therapies and elimination rates of all types of multispecies oral biofilms. In that context, integrating or even replacing conventional dental therapy protocols with herbal-inspired treatments can allow effective antimicrobial control of oral biofilms and thus, dental diseases. PMID:26834707

Natural Antimicrobials and Oral Microorganisms: A Systematic Review on Herbal Interventions for the Eradication of Multispecies Oral Biofilms.

PubMed

Karygianni, Lamprini; Al-Ahmad, Ali; Argyropoulou, Aikaterini; Hellwig, Elmar; Anderson, Annette C; Skaltsounis, Alexios L

2015-01-01

Oral diseases such as caries and periodontitis are mainly caused by microbial biofilms. Antibiotic therapy has reached its limits with regard to antimicrobial resistance, and new therapeutic measures utilizing natural phytochemicals are currently a focus of research. Hence, this systematic review provides a critical presentation of the antimicrobial effects of various medicinal herbs against in vitro, ex vivo, and in situ formed multispecies oral biofilms. Searches were performed in three English databases (PubMed, EMBASE, CAMbase) and the electronic archives of five German journals from the times of their establishment until October 10th, 2014, with the search terms "(plant extracts OR herbal extracts OR plant OR herb) AND (oral biofilm OR dental biofilm OR dental plaque OR oral disease OR dental disease)." The pooled data were assessed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Initially, 1848 articles were identified, out of which 585 full-text articles were screened, 149 articles were reevaluated for eligibility and finally, 14 articles met all inclusion criteria. The data of 14 reports disclosed enhanced antiadhesive and antibiofilm activity by the plant extracts obtained from Vitis vinifera, Pinus spp., Coffea canephora, Camellia sinensis, Vaccinium macrocarpon, Galla chinensis, Caesalpinia ferrea Martius, Psidium cattleianum, representative Brazilian plants and manuka honey. Overall, a positive correlation was revealed between herb-based therapies and elimination rates of all types of multispecies oral biofilms. In that context, integrating or even replacing conventional dental therapy protocols with herbal-inspired treatments can allow effective antimicrobial control of oral biofilms and thus, dental diseases.

Glycopeptide use is associated with increased mortality in Enterococcus faecalis bacteraemia.

PubMed

Foo, Hong; Chater, Mathew; Maley, Michael; van Hal, Sebastiaan J

2014-08-01

Enterococci are an important cause of nosocomial and community-acquired infections, with bacteraemia being one of the most common presentations. Although inappropriate antimicrobial therapy has been associated with poorer outcomes in Enterococcus faecalis (EF) bacteraemia, the impact of antimicrobial choice, namely β-lactam versus glycopeptide therapy, has not been well described. We sought to determine whether choice of antibiotic affects patient outcomes in EF bacteraemia. This retrospective cohort study was conducted at Liverpool and Bankstown Lidcombe Hospitals, Sydney, Australia between 2006 and 2013. Medical records and laboratory data for consecutive EF bacteraemias were reviewed. Clinical and microbiological data were obtained for all patients who received appropriate antimicrobial therapy with either a β-lactam or a glycopeptide antibiotic. Outcomes and predictors of mortality were determined and treatment groups were compared. One hundred and seventy-two episodes of clinically significant EF bacteraemias received appropriate antimicrobial therapy with a β-lactam (n = 126) or a glycopeptide (n = 46). All-cause 30 day mortality was 15.1%, with mortality significantly higher in patients receiving glycopeptide therapy compared with β-lactam therapy (26.1% versus 11.1%, P = 0.015). Glycopeptide therapy remained an independent predictor of 30 day mortality [OR 2.46 (95% CI 1.01-6.02), P = 0.048]. APACHE II score [OR 1.10 (95% CI 1.02-1.18), P = 0.011] and malignancy [OR 2.58 (95% CI 1.03-6.49), P = 0.044] were also independent predictors of 30 day mortality. Glycopeptide use is associated with increased mortality in patients with EF bacteraemia. In the treatment of β-lactam-susceptible EF bacteraemia, β-lactams should be considered first-line therapy. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Susceptibility of Enterococcus faecalis and Propionibacterium acnes to antimicrobial photodynamic therapy.

PubMed

de Annunzio, Sarah Raquel; de Freitas, Laura Marise; Blanco, Ana Lígia; da Costa, Mardoqueu Martins; Carmona-Vargas, Christian C; de Oliveira, Kleber Thiago; Fontana, Carla Raquel

2018-01-01

Bacterial resistance to available antibiotics nowadays is a global threat leading researchers around the world to study new treatment modalities for infections. Antimicrobial photodynamic therapy (aPDT) has been considered an effective and promising therapeutic alternative in this scenario. Briefly, this therapy is based on the activation of a non-toxic photosensitizing agent, known as photosensitizer (PS), by light at a specific wavelength generating cytotoxic singlet oxygen and free radicals. Virtually all studies related to aPDT involve a huge screening to identify ideal PS concentration and light dose combinations, a laborious and time-consuming process that is hardly disclosed in the literature. Herein, we describe an antimicrobial Photodynamic Therapy (aPDT) study against Enterococcus faecalis and Propionibacterium acnes employing methylene blue, chlorin-e6 or curcumin as PS. Similarities and discrepancies between the two bacterial species were pointed out in an attempt to speed up and facilitate futures studies against those clinical relevant strains. Susceptibility tests were performed by the broth microdilution method. Our results demonstrate that aPDT mediated by the three above-mentioned PS was effective in eliminating both gram-positive bacteria, although P. acnes showed remarkably higher susceptibility to aPDT when compared to E. faecalis. PS uptake assays revealed that P. acnes is 80 times more efficient than E. faecalis in internalizing all three PS molecules. Our results evidence that the cell wall structure is not a limiting feature when predicting bacterial susceptibility to aPDT treatment. Copyright © 2017. Published by Elsevier B.V.

Top 1% of Inpatients Administered Antimicrobial Agents Comprising 50% of Expenditures: A Descriptive Study and Opportunities for Stewardship Intervention.

PubMed

Dela-Pena, Jennifer; Kerstenetzky, Luiza; Schulz, Lucas; Kendall, Ron; Lepak, Alexander; Fox, Barry

2017-03-01

OBJECTIVE To characterize the top 1% of inpatients who contributed to the 6-month antimicrobial budget in a tertiary, academic medical center and identify cost-effective intervention opportunities targeting high-cost antimicrobial utilization. DESIGN Retrospective cohort study. PATIENTS Top 1% of the antimicrobial budget from July 1 through December 31, 2014. METHODS Patients were identified through a pharmacy billing database. Baseline characteristics were collected through a retrospective medical chart review. Patients were presented to the antimicrobial stewardship team to determine appropriate utilization of high-cost antimicrobials and potential intervention opportunities. Appropriate use was defined as antimicrobial therapy that was effective, safe, and most cost-effective compared with alternative agents. RESULTS A total of 10,460 patients received antimicrobials in 6 months; 106 patients accounted for $889,543 (47.2%) of the antimicrobial budget with an antimicrobial cost per day of $219±$192 and antimicrobial cost per admission of $4,733±$7,614. Most patients were immunocompromised (75%) and were followed by the infectious disease consult service (80%). The most commonly prescribed antimicrobials for treatment were daptomycin, micafungin, liposomal amphotericin B, and meropenem. Posaconazole and valganciclovir accounted for most of the prophylactic therapy. Cost-effective opportunities (n=71) were present in 57 (54%) of 106 patients, which included dose optimization, de-escalation, dosage form conversion, and improvement in transitions of care. CONCLUSION Antimicrobial stewardship oversight is important in implementing cost-effective strategies, especially in complex and immunocompromised patients who require the use of high-cost antimicrobials. Infect Control Hosp Epidemiol 2017;38:259-265.

Gene therapy and its implications in Periodontics

PubMed Central

Mahale, Swapna; Dani, Nitin; Ansari, Shumaila S.; Kale, Triveni

2009-01-01

Gene therapy is a field of Biomedicine. With the advent of gene therapy in dentistry, significant progress has been made in the control of periodontal diseases and reconstruction of dento-alveolar apparatus. Implementation in periodontics include: -As a mode of tissue engineering with three approaches: cell, protein-based and gene delivery approach. -Genetic approach to Biofilm Antibiotic Resistance. Future strategies of gene therapy in preventing periodontal diseases: -Enhances host defense mechanism against infection by transfecting host cells with an antimicrobial peptide protein-encoding gene. -Periodontal vaccination. Gene therapy is one of the recent entrants and its applications in the field of periodontics are reviewed in general here. PMID:20376232

Evaluation of pharmacy generalists performing antimicrobial stewardship services.

PubMed

Carreno, Joseph J; Kenney, Rachel M; Bloome, Mary; McDonnell, Jane; Rodriguez, Jennifer; Weinmann, Allison; Kilgore, Paul E; Davis, Susan L

2015-08-01

Improvements in medication use achieved by pharmacy generalists using a care bundle approach to antimicrobial stewardship are reported. A six-month prospective, repeated-treatment, quasi-experimental study involving three month-long intervention periods and three month-long control periods was conducted in the setting of an existing antimicrobial stewardship program at a large hospital. The intervention involved prospective audit and feedback conducted by pharmacy generalists who were trained in an antimicrobial stewardship care bundle approach. During control months, a pharmacy generalist who was not trained in antimicrobial stewardship rounded with the multidisciplinary team and provided standard-of-care pharmacy services. The primary endpoint was compliance with a care bundle of four antimicrobial stewardship metrics: documentation of indication for therapy in the medical record, selection of empirical therapy according to institutional guidelines, documented performance of indicated culture testing, and deescalation of therapy when indicated. Two-hundred eighty-six patients were enrolled in the study: 124 in the intervention group and 162 in the control group. The cumulative rate of full compliance with all care bundle components during the six-month study was significantly greater during intervention months than during control months (68.5% versus 45.7%, p < 0.001). After adjusting for infection type, antimicrobial stewardship provided by an intervention-group pharmacist was associated with improved care bundle compliance (adjusted odds ratio, 2.70; p < 0.001). No significant differences in patient outcomes during intervention and control months were detected. Pharmacy generalists trained to comply with a systematic care bundle approach enhanced the quality of antimicrobial management. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

The effect of pathophysiology on pharmacokinetics in the critically ill patient--concepts appraised by the example of antimicrobial agents.

PubMed

Blot, Stijn I; Pea, Federico; Lipman, Jeffrey

2014-11-20

Critically ill patients are at high risk for development of life-threatening infection leading to sepsis and multiple organ failure. Adequate antimicrobial therapy is pivotal for optimizing the chances of survival. However, efficient dosing is problematic because pathophysiological changes associated with critical illness impact on pharmacokinetics of mainly hydrophilic antimicrobials. Concentrations of hydrophilic antimicrobials may be increased because of decreased renal clearance due to acute kidney injury. Alternatively, antimicrobial concentrations may be decreased because of increased volume of distribution and augmented renal clearance provoked by systemic inflammatory response syndrome, capillary leak, decreased protein binding and administration of intravenous fluids and inotropes. Often multiple conditions that may influence pharmacokinetics are present at the same time thereby excessively complicating the prediction of adequate concentrations. In general, conditions leading to underdosing are predominant. Yet, since prediction of serum concentrations remains difficult, therapeutic drug monitoring for individual fine-tuning of antimicrobial therapy seems the way forward. Copyright © 2014. Published by Elsevier B.V.

Guidelines-concordant empiric antimicrobial therapy and mortality in patients with severe community-acquired pneumonia requiring mechanical ventilation.

PubMed

Sakamoto, Yukiyo; Yamauchi, Yasuhiro; Yasunaga, Hideo; Takeshima, Hideyuki; Hasegawa, Wakae; Jo, Taisuke; Matsui, Hiroki; Fushimi, Kiyohide; Nagase, Takahide

2017-01-01

Community-acquired pneumonia (CAP) has high morbidity and mortality among adults. Several clinical guidelines recommend prompt administration of combined antimicrobial therapy. However, the association between guidelines concordance and mortality in patients with severe pneumonia remains unclear. The present study aimed to examine the impact of guidelines-concordant empiric antimicrobial therapy on 7-day mortality in patients with extremely severe pneumonia who required mechanical ventilation at admission, using a nationwide inpatient database in Japan. Data of CAP patients aged over 20 years who required mechanical ventilation at admission between April 2012 and March 2014 were retrospectively analyzed. Multivariable logistic regression analysis was performed to examine the association between guidelines-concordant empiric antimicrobial therapy and all-cause 7-day mortality, with adjustment for patient backgrounds and pneumonia severity. There were a total of 3719 eligible patients, 836 (22.5%) of whom received guidelines-concordant combination therapy. Overall, 7-day mortality was 29.5%. Higher 7-day mortality was associated with advanced age, confusion, lower systolic blood pressure, malignant tumor or immunocompromised state, and C-reactive protein ≥20mg/dl or infiltration occupying two-thirds of one lung on chest radiography. After adjustment for these variables, guidelines-concordant combined antimicrobial therapy was associated with significantly lower 7-day mortality (odds ratio: 0.78; 95% confidence interval: 0.65-0.95; P=0.013). Adherence to initial empiric treatment as recommended by the guidelines was associated with better short-term prognosis in patients with extremely severe pneumonia who required mechanical ventilation on hospital admission. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Fifty Years of Research in ARDS. Cell-based Therapy for Acute Respiratory Distress Syndrome. Biology and Potential Therapeutic Value.

PubMed

Laffey, John G; Matthay, Michael A

2017-08-01

On the basis of several preclinical studies, cell-based therapy has emerged as a potential new therapeutic for acute respiratory distress syndrome (ARDS). Of the various cell-based therapy options, mesenchymal stem/stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord have the most experimental data to support their potential efficacy for lung injury from both infectious and noninfectious causes. Mechanistically, MSCs exert their beneficial effects by release of paracrine factors, microvesicles, and transfer of mitochondria, all of which have antiinflammatory and pro-resolving effects on injured lung endothelium and alveolar epithelium, including enhancing the resolution of pulmonary edema by up-regulating sodium-dependent alveolar fluid clearance. MSCs also have antimicrobial effects mediated by release of antimicrobial factors and by up-regulating monocyte/macrophage phagocytosis. Phase 2a clinical trials to establish safety in ARDS are in progress, and two phase 1 trials did not report any serious adverse events. Several issues need further study, including: determining the optimal methods for large-scale production, reconstitution of cryopreserved cells for clinical use, defining cell potency assays, and determining the therapeutic potential of conditioned media derived from MSCs. Because ARDS is a heterogeneous syndrome, targeting MSCs to patients with ARDS with a more hyperinflammatory endotype may further enhance their potential for efficacy.

Efficacy of Local and Systemic Antimicrobials in the Non-Surgical Treatment of Smokers With Chronic Periodontitis: A Systematic Review.

PubMed

Chambrone, Leandro; Vargas, Miguel; Arboleda, Silie; Serna, Maritza; Guerrero, Marcela; de Sousa, Jose; Lafaurie, Gloria Inés

2016-11-01

The aim of this systematic review is to evaluate whether use of local or systemic antimicrobials would improve clinical results of non-surgical periodontal therapy for smokers with chronic periodontitis (CP). Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and The Cochrane Central Register of Controlled Trials were searched up to and including March 2016. Randomized clinical trials of duration of at least 6 months were included if they reported on treatment of smokers (≥10 cigarettes per day for minimum 12 months) with CP with non-surgical periodontal therapy either alone or associated with local or systemic antimicrobials. Random-effects meta-analyses were undertaken to evaluate mean differences in probing depth (PD) and clinical attachment level (CAL). Of 108 potentially eligible articles, seven were included. Most individual studies (75%) testing locally delivered antibiotics reported that smokers benefited from this treatment approach. Pooled estimates found additional PD reduction of 0.81 mm (P = 0.01) and CAL gain of 0.91 mm (P = 0.01) at sites with baseline PD ≥5 mm. Conversely, meta-analysis on systemic use of antimicrobials failed to detect significant differences in mean changes from baseline, and only one trial supported their use. In smokers with CP, adjunctive use of local antimicrobials improved efficacy of non-surgical periodontal therapy in reducing PD and improving CAL at sites presenting PD ≥5 mm before treatment. Current evidence does not demonstrate similar gains when scaling and root planing plus systemic antimicrobial/antibiotics were associated with therapy.

Antimicrobial resistance in patients with urinary tract infections and the impact on empiric therapy in Serbia.

PubMed

Zec, Simon; Despotovic, Aleksa; Spurnic-Radovanovic, Aleksandra; Milosevic, Ivana; Jovanovic, Milica; Pelemis, Mijomir; Stevanovic, Goran

2016-10-31

Surveillance of antimicrobial resistance is essential in establishing treatment guidelines for urinary tract infections. The aim of this pilot study was to analyse resistance rates of pathogens, across different demographics and determine whether adjustments in empiric therapy should be considered for different age and gender groups. A 5-year retrospective study included 256 patients hospitalised, under the initial diagnosis of Fever of Unknown Origin who were then subsequently diagnosed with a urinary tract infection at the Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia. Patients were evaluated using demographic, clinical, and antimicrobial resistance data with appropriate statistical analysis including ANOVA significance testing, univariate, and multivariate analysis. Resistance rates were above the threshold of 20% for the majority of the antimicrobials tested, the only exception being carbapenems. Amikacin, cefepime, and norfloxacin were agents that could be effectively used as empiric therapy in younger adults with resistance rates of 4.2, 8.0, and 10.0%, respectively. Moderate resistance rates of 17.4% for amikacin and 19.1% for cefepime were observed in the age group 35-64 years. High resistance rates were observed for all antimicrobials among patients 65 years and over. Among male patients, resistance rates to most antimicrobials were high. In female patients, amikacin and cefepime had resistance rates less than 20%. Younger age presented as a negative risk factor for infection by a multi-drug resistant pathogen. Age and gender demonstrated to be significant factors for determining proper empiric therapy; large-scale studies from Serbia are needed to solidify these findings.

Nanomaterials for alternative antibacterial therapy

PubMed Central

Hemeg, Hassan A

2017-01-01

Despite an array of cogent antibiotics, bacterial infections, notably those produced by nosocomial pathogens, still remain a leading factor of morbidity and mortality around the globe. They target the severely ill, hospitalized and immunocompromised patients with incapacitated immune system, who are prone to infections. The choice of antimicrobial therapy is largely empirical and not devoid of toxicity, hypersensitivity, teratogenicity and/or mutagenicity. The emergence of multidrug-resistant bacteria further intensifies the clinical predicament as it directly impacts public health due to diminished potency of current antibiotics. In addition, there is an escalating concern with respect to biofilm-associated infections that are refractory to the presently available antimicrobial armory, leaving almost no therapeutic option. Hence, there is a dire need to develop alternate antibacterial agents. The past decade has witnessed a substantial upsurge in the global use of nanomedicines as innovative tools for combating the high rates of antimicrobial resistance. Antibacterial activity of metal and metal oxide nanoparticles (NPs) has been extensively reported. The microbes are eliminated either by microbicidal effects of the NPs, such as release of free metal ions culminating in cell membrane damage, DNA interactions or free radical generation, or by microbiostatic effects coupled with killing potentiated by the host’s immune system. This review encompasses the magnitude of multidrug resistance in nosocomial infections, bacterial evasion of the host immune system, mechanisms used by bacteria to develop drug resistance and the use of nanomaterials based on metals to overcome these challenges. The diverse annihilative effects of conventional and biogenic metal NPs for antibacterial activity are also discussed. The use of polymer-based nanomaterials and nanocomposites, alone or functionalized with ligands, antibodies or antibiotics, as alternative antimicrobial agents for treating severe bacterial infections is also discussed. Combinatorial therapy with metallic NPs, as adjunct to the existing antibiotics, may aid to restrain the mounting menace of bacterial resistance and nosocomial threat. PMID:29184409

Ertapenem: a new opportunity for outpatient parenteral antimicrobial therapy.

PubMed

Tice, Alan D

2004-06-01

Ertapenem is a parenteral carbapenem antimicrobial with pharmacological properties that allow it to be given once daily. This makes it a consideration for outpatient parenteral antimicrobial therapy (OPAT). In comparison with information from the OPAT Outcomes Registry, ertapenem seems well suited for the types of infections and bacteria that are commonly treated with OPAT, plus it has additional activity against anaerobic bacteria. This added spectrum makes it possible to treat complicated skin/skin-structure, complicated intra-abdominal and pelvic infections with a single antibiotic instead of the multiple agents that have usually been required. Ertapenem is also comparable to other OPAT antimicrobials in terms of adverse effects and clinical outcomes. This antimicrobial can be given with any delivery model, although its stability when mixed is such that daily preparation or self-mixing systems need to be considered. Ertapenem should be added to the growing list of once-daily parenteral antibiotics that can be given to outpatients.

Behavioral Approach to Appropriate Antimicrobial Prescribing in Hospitals: The Dutch Unique Method for Antimicrobial Stewardship (DUMAS) Participatory Intervention Study.

PubMed

Sikkens, Jonne J; van Agtmael, Michiel A; Peters, Edgar J G; Lettinga, Kamilla D; van der Kuip, Martijn; Vandenbroucke-Grauls, Christina M J E; Wagner, Cordula; Kramer, Mark H H

2017-08-01

Inappropriate antimicrobial prescribing leads to antimicrobial resistance and suboptimal clinical outcomes. Changing antimicrobial prescribing is a complex behavioral process that is not often taken into account in antimicrobial stewardship programs. To examine whether an antimicrobial stewardship approach grounded in behavioral theory and focusing on preserving prescriber autonomy and participation is effective in improving appropriateness of antimicrobial prescribing in hospitals. The Dutch Unique Method for Antimicrobial Stewardship (DUMAS) study was a prospective, stepped-wedge, participatory intervention study performed from October 1, 2011, through December 31, 2015. Outcomes were measured during a baseline period of 16 months and an intervention period of 12 months. The study was performed at 7 clinical departments (2 medical, 3 surgical, and 2 pediatric) in a tertiary care medical center and a general teaching hospital in the Netherlands. Physicians prescribing systemic antimicrobial drugs for any indication for patients admitted to the participating departments during the study period were included in the study. We offered prescribers a free choice of how to improve their antimicrobial prescribing. Prescribers were stimulated to choose interventions with higher potential for success based on a root cause analysis of inappropriate prescribing. Appropriateness of antimicrobial prescriptions was determined using a validated approach based on guideline adherence and motivated guideline deviation and measured with repeated point prevalence surveys (6 per year). Appropriateness judgment was masked for the study period. Antimicrobial consumption was extracted from pharmacy records and measured as days of therapy per admission. We used linear and logistic mixed-model regression analysis to model outcomes over time. A total of 1121 patient cases with 700 antimicrobial prescriptions were assessed during the baseline period and 882 patient cases with 531 antimicrobial prescriptions during the intervention period. The mean antimicrobial appropriateness increased from 64.1% at intervention start to 77.4% at 12-month follow-up (+13.3%; relative risk, 1.17; 95% CI, 1.04-1.27), without a change in slope. No decrease in antimicrobial consumption was found. Use of a behavioral approach preserving prescriber autonomy resulted in an increase in antimicrobial appropriateness sustained for at least 12 months. The approach is inexpensive and could be easily transferable to various health care environments.

Factors influencing antimicrobial prescribing by veterinarians and usage by dairy farmers in New Zealand.

PubMed

McDougall, S; Compton, Cwr; Botha, N

2017-03-01

To determine the factors associated with the selection of antimicrobials by dairy veterinarians, and the attitudes of those veterinarians and dairy farmers to antimicrobial usage and resistance. Facilitated focus groups of dairy farmers (n=22) and an anonymous online survey of dairy cattle veterinarians (n=206 respondents) were used to determine prescribing behaviour, factors affecting prescribing of antimicrobials, and the attitudes of veterinarians and farmers to the use of antimicrobials and the risk of antimicrobial resistance (AMR). Amongst the 22 farmers, the most common primary reason for choosing an antimicrobial was veterinary advice (87%) followed by personal experience (68%). Farmers had limited knowledge or concern about the risk of AMR, particularly outside their farm, with only 47% and 26% agreeing or strongly agreeing that use of antimicrobials on their farm would increase the risk of resistance in their herd and in humans, respectively. Prescribing of antimicrobials by veterinarians was predominantly based on diagnosis (168/206; 82%), and response to previous therapy (134/206; 65%), while duration above the minimum inhibitory concentration (43/206; 21%) was also considered important. Non-clinical factors such as withholding period (52/206; 25%) and farmers' preferences (45/206; 22%) also influenced prescribing. Antimicrobial culture and susceptibility testing was not widely used, with 126/166 (76%) having culture results for less than four of the last 10 clinical mastitis cases for which they prescribed antimicrobials. Attitudes about prescribing and AMR varied with years of practice, gender and employment status. Veterinarians primarily considered technical reasons when prescribing antimicrobials. However non-technical factors did influence prescribing, in particular client feedback about perceived efficacy and perceptions of cost/benefit. Farmers stated that veterinarians were the most credible source of advice for selection of antimicrobials, but that personal experience on their farm was also important. Farmers' perception of efficacy of antimicrobials, based on clinical outcomes, is an important determinant of their preferred choice of product. Hence, where changes in on-farm use patterns are required, clear communication by veterinarians about prudent antimicrobial choice and usage will require initial education around classes of antimicrobials and risk of resistance, as well as information around assessing efficacy of antimicrobial usage. Many veterinarians are in businesses that do not have practice prescribing policies. Such policies would likely lead to more consistent and judicious use of antimicrobials.

Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors.

PubMed

Hanski, Leena; Vuorela, Pia

2016-11-28

Throughout its known history, the gram-negative bacterium Chlamydia pneumoniae has remained a challenging target for antibacterial chemotherapy and drug discovery. Owing to its well-known propensity for persistence and recent reports on antimicrobial resistence within closely related species, new approaches for targeting this ubiquitous human pathogen are urgently needed. In this review, we describe the strategies that have been successfully applied for the identification of nonconventional antichlamydial agents, including target-based and ligand-based virtual screening, ethnopharmacological approach and pharmacophore-based design of antimicrobial peptide-mimicking compounds. Among the antichlamydial agents identified via these strategies, most translational work has been carried out with plant phenolics. Thus, currently available data on their properties as antichlamydial agents are described, highlighting their potential mechanisms of action. In this context, the role of mitogen-activated protein kinase activation in the intracellular growth and survival of C . pneumoniae is discussed. Owing to the complex and often complementary pathways applied by C. pneumoniae in the different stages of its life cycle, multitargeted therapy approaches are expected to provide better tools for antichlamydial therapy than agents with a single molecular target.

Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors

PubMed Central

Hanski, Leena; Vuorela, Pia

2016-01-01

Throughout its known history, the gram-negative bacterium Chlamydia pneumoniae has remained a challenging target for antibacterial chemotherapy and drug discovery. Owing to its well-known propensity for persistence and recent reports on antimicrobial resistence within closely related species, new approaches for targeting this ubiquitous human pathogen are urgently needed. In this review, we describe the strategies that have been successfully applied for the identification of nonconventional antichlamydial agents, including target-based and ligand-based virtual screening, ethnopharmacological approach and pharmacophore-based design of antimicrobial peptide-mimicking compounds. Among the antichlamydial agents identified via these strategies, most translational work has been carried out with plant phenolics. Thus, currently available data on their properties as antichlamydial agents are described, highlighting their potential mechanisms of action. In this context, the role of mitogen-activated protein kinase activation in the intracellular growth and survival of C. pneumoniae is discussed. Owing to the complex and often complementary pathways applied by C. pneumoniae in the different stages of its life cycle, multitargeted therapy approaches are expected to provide better tools for antichlamydial therapy than agents with a single molecular target. PMID:27916800

Qualitative study of factors associated with antimicrobial usage in seven small animal veterinary practices in the UK.

PubMed

Mateus, Ana L P; Brodbelt, David C; Barber, Nick; Stärk, Katharina D C

2014-11-01

Responsible use of antimicrobials by veterinarians is essential to contain antimicrobial resistance in pathogens relevant to public health. Inappropriate antimicrobial use has been previously described in practice. However, there is scarce information on factors influencing antimicrobial usage in dogs and cats. We investigated intrinsic and extrinsic factors influencing decision-making of antimicrobial usage in first opinion small animal practices in the UK through the application of qualitative research methods. Semi-structured interviews were conducted with 21 veterinarians from seven veterinary first opinion practices in the UK in 2010. Topics investigated included: a) criteria used for selection of antimicrobials, b) influences by colleagues, c) influences by clients, d) pet characteristics, e) sources of knowledge, f) awareness of guidelines and g) protocols implemented in practice that may affect antimicrobial usage by veterinarians. Hypothetical scenarios selected to assess appropriateness of antimicrobial usage were: a) vomiting in a Yorkshire Terrier due to dietary indiscretion, b) deep pyoderma in a Shar-Pei, c) Feline Lower Urinary Tract disease in an 7 year-old male neutered cat and d) neutering of a 6-months dog. Interviews were recorded and transcribed by the interviewer. Thematic analysis was used to analyse content of transcribed interviews. Data management and analysis was conducted with qualitative analysis software NVivo8 (QSR International Pty Ltd). Antimicrobial usage by participants was influenced by factors other than clinical evidence and scientific knowledge. Intrinsic factors included veterinarian's preference of substances and previous experience. Extrinsic factors influencing antimicrobial selection were; perceived efficacy, ease of administration of formulations, perceived compliance, willingness and ability to treat by pet owners, and animal characteristics. Cost of therapy was only perceived as an influential factor in low, mixed socioeconomic areas. Veterinarians had limited awareness of current recommendations for responsible use in small animal practice. Social norms, particularly verbally agreed protocols influenced veterinarians. Inappropriate antimicrobial usage was identified in the therapy of non-infectious diseases and prophylaxis of routine clean surgical procedures. Discussion of clinical cases with peers and effectiveness meetings in the workplace were useful to veterinarians to share scientific knowledge. Effectiveness meetings can be a common ground for veterinarians to discuss and agree protocols for clinical conditions and surgical procedures. Protocols should be evidence-based, follow current recommendations and take into account the resources available in the workplace. Targeted training of veterinarians in the workplace with peer support should be used to promote responsible antimicrobial usage. Copyright © 2014 Elsevier B.V. All rights reserved.

Functional synergy of α-helical antimicrobial peptides and traditional antibiotics against Gram-negative and Gram-positive bacteria in vitro and in vivo.

PubMed

Feng, Q; Huang, Y; Chen, M; Li, G; Chen, Y

2015-01-01

In this study, the antimicrobial activities based on the synergistic effects of traditional antibiotics (imipenem, cefepime, levofloxacin hydrochloride and vancomycin) and antimicrobial peptides (AMPs; PL-5, PL-31, PL-32, PL-18, PL-29 and PL-26), alone or in combination, against three Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae and Staphylococcus epidermidis) and three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae) were investigated. In addition, the antimicrobial activity that was based on the synergistic effects of levofloxacin hydrochloride and PL-5 against Staphylococcus aureus in vivo was explored in a mouse infection model. Traditional antibiotics and AMPs showed significant synergistic effects on the antibacterial activities against the different Gram-positive and Gram-negative bacteria in vitro. A strong synergistic effect in the PL-5 and levofloxacin hydrochloride combination against Staphylococcus aureus was observed in the mouse infection model in vivo. The mechanism of synergistic action was due to the different targets of AMPs and traditional antibiotics. The combination of AMPs and traditional antibiotics can dramatically enhance antimicrobial activity and may help prevent or delay the emergence of antibiotic resistance. Thus, this combination therapy could be a promising approach to treat bacterial infections, particularly mixed infections and multi-antibiotic-resistant infections, in the clinics.

Impact of antimicrobial stewardship programme on hospitalized patients at the intensive care unit: a prospective audit and feedback study.

PubMed

Khdour, Maher R; Hallak, Hussein O; Aldeyab, Mamoon A; Nasif, Mowaffaq A; Khalili, Aliaa M; Dallashi, Ahamad A; Khofash, Mohammad B; Scott, Michael G

2018-04-01

Inappropriate use of antibiotics is one of the most important factors contributing to the emergence of drug resistant pathogens. The purpose of this study was to measure the clinical impact of antimicrobial stewardship programme (ASP) interventions on hospitalized patients at the Intensive care unit at Palestinian Medical Complex. A prospective audit with intervention and feedback by ASP team within 48-72 h of antibiotic administration began in September 2015. Four months of pre-ASP data were compared with 4 months of post-ASP data. Data collected included clinical and demographic data; use of antimicrobials measured by defined daily doses, duration of therapy, length of stay, readmission and all-cause mortality. Overall, 176 interventions were made the ASP team with an average acceptance rate of 78.4%. The most accepted interventions were dose optimization (87.0%) followed by de-escalation based on culture results with an acceptance rate of 84.4%. ASP interventions significantly reduces antimicrobial use by 24.3% (87.3 defined daily doses/100 beds vs. 66.1 defined daily doses/100 beds P < 0.001). The median (interquartile range) of length of stay was significantly reduced post ASP [11 (3-21) vs. 7 (4-19) days; P < 0.01]. Also, the median (interquartile range) of duration of therapy was significantly reduced post-ASP [8 (5-12) days vs. 5 (3-9); P = 0.01]. There was no significant difference in overall 30-day mortality or readmission between the pre-ASP and post-ASP groups (26.9% vs. 23.9%; P = 0.1) and (26.1% vs. 24.6%; P = 0.54) respectively. Our prospective audit and feedback programme was associated with positive impact on antimicrobial use, duration of therapy and length of stay. © 2017 The British Pharmacological Society.

Management of established pressure ulcer infections in spinal cord injury patients.

PubMed

Dinh, A; Bouchand, F; Davido, B; Duran, C; Denys, P; Lortat-Jacob, A; Rottman, M; Salomon, J; Bernard, L

2018-06-21

Pressure ulcers are frequently observed in spinal cord injury (SCI) patients. They can be life-threatening and are a major medico-economic burden. Despite their frequency, their pathophysiology and optimal management are still poorly understood. Most available data comes from non-comparative studies, especially in terms of antimicrobial use. We performed a critical review of the literature and opinions of infectious disease specialists based in a French expert center for this disease. We mainly focused on antimicrobial treatments prescribed in this situation. These infections are usually clinically diagnosed. Microbiological samples are not the gold standard for this assessment. Furthermore, reliable microbiological identification is a major challenge but should help select antimicrobial treatment. Imaging technique could be helpful but cannot replace the physical examination. The choice of antimicrobials must consider the potential ecological collateral damages in this vulnerable population. Antimicrobial therapy should be as short as possible, adapted to the microbiological identification, and must have suitable bioavailability. Management of infected pressure ulcers is a major concern in disabled patients already highly exposed to antimicrobial treatment and multidrug-resistant organisms colonization. Extensive data is required. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Behavioral Approach to Appropriate Antimicrobial Prescribing in Hospitals

PubMed Central

van Agtmael, Michiel A.; Peters, Edgar J. G.; Lettinga, Kamilla D.; van der Kuip, Martijn; Vandenbroucke-Grauls, Christina M. J. E.; Wagner, Cordula; Kramer, Mark H. H.

2017-01-01

Importance Inappropriate antimicrobial prescribing leads to antimicrobial resistance and suboptimal clinical outcomes. Changing antimicrobial prescribing is a complex behavioral process that is not often taken into account in antimicrobial stewardship programs. Objective To examine whether an antimicrobial stewardship approach grounded in behavioral theory and focusing on preserving prescriber autonomy and participation is effective in improving appropriateness of antimicrobial prescribing in hospitals. Design, Setting, and Participants The Dutch Unique Method for Antimicrobial Stewardship (DUMAS) study was a prospective, stepped-wedge, participatory intervention study performed from October 1, 2011, through December 31, 2015. Outcomes were measured during a baseline period of 16 months and an intervention period of 12 months. The study was performed at 7 clinical departments (2 medical, 3 surgical, and 2 pediatric) in a tertiary care medical center and a general teaching hospital in the Netherlands. Physicians prescribing systemic antimicrobial drugs for any indication for patients admitted to the participating departments during the study period were included in the study. Interventions We offered prescribers a free choice of how to improve their antimicrobial prescribing. Prescribers were stimulated to choose interventions with higher potential for success based on a root cause analysis of inappropriate prescribing. Main Outcomes and Measures Appropriateness of antimicrobial prescriptions was determined using a validated approach based on guideline adherence and motivated guideline deviation and measured with repeated point prevalence surveys (6 per year). Appropriateness judgment was masked for the study period. Antimicrobial consumption was extracted from pharmacy records and measured as days of therapy per admission. We used linear and logistic mixed-model regression analysis to model outcomes over time. Results A total of 1121 patient cases with 700 antimicrobial prescriptions were assessed during the baseline period and 882 patient cases with 531 antimicrobial prescriptions during the intervention period. The mean antimicrobial appropriateness increased from 64.1% at intervention start to 77.4% at 12-month follow-up (+13.3%; relative risk, 1.17; 95% CI, 1.04-1.27), without a change in slope. No decrease in antimicrobial consumption was found. Conclusions and Relevance Use of a behavioral approach preserving prescriber autonomy resulted in an increase in antimicrobial appropriateness sustained for at least 12 months. The approach is inexpensive and could be easily transferable to various health care environments. PMID:28459929

Reprogrammable microbial cell-based therapeutics against antibiotic-resistant bacteria.

PubMed

Hwang, In Young; Koh, Elvin; Kim, Hye Rim; Yew, Wen Shan; Chang, Matthew Wook

2016-07-01

The discovery of antimicrobial drugs and their subsequent use has offered an effective treatment option for bacterial infections, reducing morbidity and mortality over the past 60 years. However, the indiscriminate use of antimicrobials in the clinical, community and agricultural settings has resulted in selection for multidrug-resistant bacteria, which has led to the prediction of possible re-entrance to the pre-antibiotic era. The situation is further exacerbated by significantly reduced antimicrobial drug discovery efforts by large pharmaceutical companies, resulting in a steady decline in the number of new antimicrobial agents brought to the market in the past several decades. Consequently, there is a pressing need for new antimicrobial therapies that can be readily designed and implemented. Recently, it has become clear that the administration of broad-spectrum antibiotics can lead to collateral damage to the human commensal microbiota, which plays several key roles in host health. Advances in genetic engineering have opened the possibility of reprogramming commensal bacteria that are in symbiotic existence throughout the human body to implement antimicrobial drugs with high versatility and efficacy against pathogenic bacteria. In this review, we discuss recent advances and potentialities of engineered bacteria in providing a novel antimicrobial strategy against antibiotic resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Antibiotic therapy of hospital-acquired pneumonia and its pharmacoeconomics].

PubMed

Kolář, Milan; Htoutou Sedláková, Miroslava; Urbánek, Karel; Uvízl, Radomír; Adamus, Milan; Imwensi, O P

2016-03-01

Important hospital-acquired infections include pneumonia, mainly because of the increasing resistance of bacterial pathogens to antimicrobials and the associated potential failure of antibiotic therapy. The present study aimed at determining the most frequent etiological agents of hospital-acquired pneumonia (HAP) and assessing the relationship between 30-day mortality and adequacy of antibiotic therapy. Based on the obtained information, optimal patterns of antibiotic therapy were to be defined, including a pharmacoeconomic perspective. In patients with clinically confirmed HAP, bacterial etiological agents were identified, their susceptibility to antimicrobials was determined and statistical methods were used to assess the relationship between adequacy of antibiotic therapy and 30-day mortality. The study comprised 68 patients with clinically confirmed HAP. The most common etiological agents were strains of Pseudomonas aeruginosa (30.8 %), Klebsiella pneumoniae (23.1 %) and Burkholderia cepacia complex (15.4 %). Gram-negative bacteria accounted for 86.5 % of all bacterial pathogens. The overall mortality reached 42.5 %. In the subgroup of patients with inadequate antibiotic therapy, 30-day mortality was significantly higher (83.3 %) than in the subgroup with adequate therapy (30.0 %; p = 0.002). The risk for 30-day mortality was 2.78 times higher in case of inadequate antibiotic therapy (95%CI: 1.52-5.07). The proportion of Pseudomonas aeruginosa strains was significantly higher in the subgroup of patients with inadequate antibiotic therapy than in those with adequate therapy (67 % vs. 27 %; p = 0.032). Results of the present study suggest a significant relationship between mortality of patients with HAP and ineffective antibiotic therapy due to resistance of the bacterial pathogen. Thus, it is clear that initial antibiotic therapy must be based on qualified assumption of sufficient activity against the most common bacterial pathogens and results of surveillance of bacterial resistance in the relevant epidemiological unit. At the same time, however, it must be stressed that it is impossible to cover all potential variants of the etiological agents and their resistance phenotypes.

Beta-Lactamase Repressor BlaI Modulates Staphylococcus aureus Cathelicidin Antimicrobial Peptide Resistance and Virulence.

PubMed

Pence, Morgan A; Haste, Nina M; Meharena, Hiruy S; Olson, Joshua; Gallo, Richard L; Nizet, Victor; Kristian, Sascha A

2015-01-01

BlaI is a repressor of BlaZ, the beta-lactamase responsible for penicillin resistance in Staphylococcus aureus. Through screening a transposon library in S. aureus Newman for susceptibility to cathelicidin antimicrobial peptide, we discovered BlaI as a novel cathelicidin resistance factor. Additionally, through integrational mutagenesis in S. aureus Newman and MRSA Sanger 252 strains, we confirmed the role of BlaI in resistance to human and murine cathelidicin and showed that it contributes to virulence in human whole blood and murine infection models. We further demonstrated that BlaI could be a target for innate immune-based antimicrobial therapies; by removing BlaI through subinhibitory concentrations of 6-aminopenicillanic acid, we were able to sensitize S. aureus to LL-37 killing.

Alternatives to overcoming bacterial resistances: State-of-the-art.

PubMed

Rios, Alessandra C; Moutinho, Carla G; Pinto, Flávio C; Del Fiol, Fernando S; Jozala, Angela; Chaud, Marco V; Vila, Marta M D C; Teixeira, José A; Balcão, Victor M

2016-10-01

Worldwide, bacterial resistance to chemical antibiotics has reached such a high level that endangers public health. Presently, the adoption of alternative strategies that promote the elimination of resistant microbial strains from the environment is of utmost importance. This review discusses and analyses several (potential) alternative strategies to current chemical antibiotics. Bacteriophage (or phage) therapy, although not new, makes use of strictly lytic phage particles as an alternative, or a complement, in the antimicrobial treatment of bacterial infections. It is being rediscovered as a safe method, because these biological entities devoid of any metabolic machinery do not possess any affinity whatsoever to eukaryotic cells. Lysin therapy is also recognized as an innovative antimicrobial therapeutic option, since the topical administration of preparations containing purified recombinant lysins with amounts in the order of nanograms, in infections caused by Gram-positive bacteria, demonstrated a high therapeutic potential by causing immediate lysis of the target bacterial cells. Additionally, this therapy exhibits the potential to act synergistically when combined with certain chemical antibiotics already available on the market. Another potential alternative antimicrobial therapy is based on the use of antimicrobial peptides (AMPs), amphiphilic polypeptides that cause disruption of the bacterial membrane and can be used in the treatment of bacterial, fungal and viral infections, in the prevention of biofilm formation, and as antitumoral agents. Interestingly, bacteriocins are a common strategy of bacterial defense against other bacterial agents, eliminating the potential opponents of the former and increasing the number of available nutrients in the environment for their own growth. They can be applied in the food industry as biopreservatives and as probiotics, and also in fighting multi-resistant bacterial strains. The use of antibacterial antibodies promises to be extremely safe and effective. Additionally, vaccination emerges as one of the most promising preventive strategies. All these will be tackled in detail in this review paper. Copyright © 2016. Published by Elsevier GmbH.

Ocular surface infections in northeastern state of malaysia: a 10-year review of bacterial isolates and antimicrobial susceptibility.

PubMed

Rahman, Zaidah A; Harun, Azian; Hasan, Habsah; Mohamed, Zeehaida; Noor, Siti S Md; Deris, Zakuan Z; Ismail, Nabilah; Hassan, Asma S; Ahmad, Fadzhilah; Yaakub, Azhany

2013-09-01

Ocular surface infections that include infections of conjunctiva, adnexa, and cornea have the potential risk of causing blindness within a given population. Empirical antibiotic therapy is usually initiated based on epidemiological data of common causative agents. Thus, the aims of this study were to determine the bacterial agents and their susceptibility patterns of isolates from ocular surface specimens in our hospital. This is a retrospective analysis and records of bacterial isolates from ocular surface specimens in Hospital Universiti Sains Malaysia from January 2001 to December 2010 were examined. Specimens were processed according to standard laboratory procedures. Antimicrobial susceptibility testing was conducted based on Clinical and Laboratory Standards Institute recommendations. Only single, nonrepetitive isolates were included in the analysis. A total of 1,267 isolates were obtained during the study period, which comprised Staphylococcus aureus (n = 299, 23.6%), Pseudomonas aeruginosa (n = 194, 15.3%), Streptococcus pneumoniae (n = 108, 8.5%), Haemophilus influenzae (n = 100, 7.9%), Haemophilus parainfluenzae (n = 84, 6.6%), and Enterobacter spp. (n = 81, 6.4%). Fungi contributed to 4.4% of the total isolates. The antimicrobial susceptibility testing demonstrated that gram-positive bacteria were generally resistant to gentamicin (19%-57%), whereas gram-negative bacteria were resistant to chloramphenicol (27%-58%). Based on the above results, knowledge of the initial Gram stain findings is imperative before the commencement of empirical antibiotic therapy. Therefore, a simple Gram staining for all eye specimens is highly recommended.

Current Trend of Antimicrobial Prescription for Oral Implant Surgery Among Dentists in India.

PubMed

Datta, Rahul; Grewal, Yasmin; Batth, J S; Singh, Amandeep

2014-12-01

The aim of our study was to evaluate antimicrobial prescription behaviour amongst dentists performing oral implant surgery in India. Dentists performing oral implant surgery from different parts of India were personally approached during various national events such as conferences and academic meetings and information regarding their prescription habits for antimicrobial agents in routine oral implant surgery was collected using a structured questionnaire. Out of a total sample of 332 dentists, 85.5 % prescribed 17 different groups or combinations of antibiotics routinely for oral implant surgery in the normal healthy patient. Majority preferred the peri-operative protocol of drug therapy (72.2 %) with variable and prolonged duration of therapy after surgery, ranging from 3 to 10 days. An antimicrobial mouthwash was routinely prescribed by all the doctors (14.5 %) not in favour of prescribing antimicrobials in a normal healthy patient. Our findings suggest that there is a trend of antimicrobial agent misuse by dentists performing oral implant surgery in India, both in terms of drugs used and the protocols prescribed. The majority of these dentists prescribed a variety of antimicrobial agents for prolonged durations routinely even in the normal, healthy patients.

Urinary Tract Infections in the Older Adult.

PubMed

Nicolle, Lindsay E

2016-08-01

Urinary infection is the most common bacterial infection in elderly populations. The high prevalence of asymptomatic bacteriuria in both men and women is benign and should not be treated. A diagnosis of symptomatic infection for elderly residents of long-term care facilities without catheters requires localizing genitourinary findings. Symptomatic urinary infection is overdiagnosed in elderly bacteriuric persons with nonlocalizing clinical presentations, with substantial inappropriate antimicrobial use. Residents with chronic indwelling catheters experience increased morbidity from urinary tract infection. Antimicrobial therapy is selected based on clinical presentation, patient tolerance, and urine culture results. Copyright © 2016 Elsevier Inc. All rights reserved.

A Mixed-Methods Pilot Study to Assess Perceptions of Antimicrobial Stewardship in Nursing Homes

PubMed Central

Carter, Rebecca R.; Montpetite, Michelle M.; Jump, Robin L. P.

2016-01-01

Objectives Practicing antimicrobial stewardship in nursing homes faces many challenges, particularly in non-academic settings. We sought to identify features of community nursing home environments that are associated with lower rates of overall antibiotic use. Design In this pilot study, we used an explanatory sequential design that incorporated comparative feedback about antibiotic use to inform a discussion about antimicrobial stewardship practices among community nursing homes. Measurements For the quantitative phase, we measured the number of antibiotic prescriptions, length of therapy and days of therapy/1000 days of care at 6 nursing homes. For the qualitative phase, we conducted semi-structured interviews with healthcare workers in leadership positions at 5 community nursing homes. Transcripts from the recorded interviews were assessed using emergent thematic analysis. For the triangulation phase, we evaluated themes from the semi-structured interviews in the context of each NHs antibiotic use. Results The number of antibiotic prescriptions ranged from 172 to 1244, with 50% to 83% written for ≤ 7 days. All nursing homes reported a similar proportion of fluoroquinolone use (27–32% days of therapy). Triangulation yielded 6 themes for which the environment at each facility ranged from less to more supportive antimicrobial stewardship: practice patterns, external influences, infection control, leadership, communication and facility culture. All nursing homes reported pressure from well-intentioned family members to prescribe antibiotics. Nursing homes with shorter lengths of therapy and lower overall antibiotic use were consonant with an environment more supportive of antimicrobial stewardship. Conclusion Our findings suggest several features of nursing homes that are supportive of antimicrobial stewardship: practice patterns grounded in established diagnostic criteria, proactive infection control and prevention, open communication and interconnectedness among staff. PMID:28152171

Inadequate treatment of ventilator-associated pneumonia: risk factors and impact on outcomes.

PubMed

Teixeira, P J Z; Seligman, R; Hertz, F T; Cruz, D B; Fachel, J M G

2007-04-01

Initial antibiotic therapy is an important determinant of clinical outcomes in ventilator-associated pneumonia (VAP). Several studies have investigated this issue, with conflicting results. This study investigated risk factors of inadequate empirical antimicrobial therapy and its impact on outcomes for patients with a clinical diagnosis of VAP. The primary outcome was adequacy of antimicrobial therapy. Secondary outcomes were duration of mechanical ventilation, hospital and intensive care unit (ICU) lengths of stay, and mortality due to VAP. Mean age was 62.9+/-15.2 years, mean APACHE (Acute Physiological Assessment and Chronic Health Evaluation) II score was 20.1+/-8.1 and mean MODS (Multiple Organ Dysfunction Score) was 3.7+/-2.5. Sixty-nine (45.7%) of 151 patients with a clinical diagnosis of VAP received inadequate antimicrobial treatment for VAP initially. There were 100 (66.2%) episodes of VAP caused by multidrug-resistant pathogens, of which 56% were inadequately treated, whereas the rate of inadequate antimicrobial therapy for VAP caused by susceptible-drug pathogens was 25.5% (P<0.001). Multiple logistic regression analysis revealed that the risk of inadequate antimicrobial treatment was more than twice as great for patients with late-onset VAP [odds ratio (OR), 2.93; 95% confidence interval (CI), 1.30-6.64; P=0.01], and more than three times for patients with VAP caused by multidrug-resistant pathogens (OR, 3.07; 95% CI, 1.29-7.30; P=0.01) or with polymicrobial VAP (OR, 3.67; 95% CI, 1.21-11.12; P=0.02). Inadequate antimicrobial treatment was associated with higher mortality for patients with VAP. Two of three independent risk factors for treatment inadequacy were associated with the isolation and identification of micro-organisms.

Whole-Genome Sequencing for Detecting Antimicrobial Resistance in Nontyphoidal Salmonella

PubMed Central

Tyson, Gregory H.; Kabera, Claudine; Chen, Yuansha; Li, Cong; Folster, Jason P.; Ayers, Sherry L.; Lam, Claudia; Tate, Heather P.; Zhao, Shaohua

2016-01-01

Laboratory-based in vitro antimicrobial susceptibility testing is the foundation for guiding anti-infective therapy and monitoring antimicrobial resistance trends. We used whole-genome sequencing (WGS) technology to identify known antimicrobial resistance determinants among strains of nontyphoidal Salmonella and correlated these with susceptibility phenotypes to evaluate the utility of WGS for antimicrobial resistance surveillance. Six hundred forty Salmonella of 43 different serotypes were selected from among retail meat and human clinical isolates that were tested for susceptibility to 14 antimicrobials using broth microdilution. The MIC for each drug was used to categorize isolates as susceptible or resistant based on Clinical and Laboratory Standards Institute clinical breakpoints or National Antimicrobial Resistance Monitoring System (NARMS) consensus interpretive criteria. Each isolate was subjected to whole-genome shotgun sequencing, and resistance genes were identified from assembled sequences. A total of 65 unique resistance genes, plus mutations in two structural resistance loci, were identified. There were more unique resistance genes (n = 59) in the 104 human isolates than in the 536 retail meat isolates (n = 36). Overall, resistance genotypes and phenotypes correlated in 99.0% of cases. Correlations approached 100% for most classes of antibiotics but were lower for aminoglycosides and beta-lactams. We report the first finding of extended-spectrum β-lactamases (ESBLs) (blaCTX-M1 and blaSHV2a) in retail meat isolates of Salmonella in the United States. Whole-genome sequencing is an effective tool for predicting antibiotic resistance in nontyphoidal Salmonella, although the use of more appropriate surveillance breakpoints and increased knowledge of new resistance alleles will further improve correlations. PMID:27381390

Appropriate antimicrobial therapy in the era of multidrug-resistant human pathogens.

PubMed

Pogue, J M; Kaye, K S; Cohen, D A; Marchaim, D

2015-04-01

The past decade has brought a significant rise in antimicrobial resistance, and the ESKAPE pathogens have become a significant threat to public health. Three epidemiological features that negatively impact patients, which are consistently seen with the ESKAPE pathogens, are the following: 1) there has been a rise in incidence of these organisms as causative human pathogens, 2) there has been a significant increase in antimicrobial resistance in these bacterial species, and 3) the infections caused by these resistant strains are associated with worse outcomes when compared with infections caused by their susceptible counterparts. Significant delays in time to appropriate antimicrobial therapy of up to 5 days have been reported in infections due to these organisms and this is the strongest predictor of mortality with ESKAPE pathogens, particular in critically ill patients, where every hour delay has an incremental survival disadvantage for patients. Strategies to decrease these delays are urgently needed. Although routine broad-spectrum empiric coverage for these organisms would ideally limit this delay, agents with activity against these organisms are sometimes less effective, have significant toxicity risk, and their use can result in the development of resistance. Therefore, strategies to optimize therapy, although limiting unnecessary use of broad-spectrum antimicrobials, are urgently needed. This review will discuss potential strategies to optimize empiric therapy in the age of multi-drug resistance, the limitations of these strategies, and will discuss future directions and opportunities. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Impact of Gram stain results on initial treatment selection in patients with ventilator-associated pneumonia: a retrospective analysis of two treatment algorithms.

PubMed

Yoshimura, Jumpei; Kinoshita, Takahiro; Yamakawa, Kazuma; Matsushima, Asako; Nakamoto, Naoki; Hamasaki, Toshimitsu; Fujimi, Satoshi

2017-06-19

Ventilator-associated pneumonia (VAP) is a common and serious problem in intensive care units (ICUs). Several studies have suggested that the Gram stain of endotracheal aspirates is a useful method for accurately diagnosing VAP. However, the usefulness of the Gram stain in predicting which microorganisms cause VAP has not been established. The purpose of this study was to evaluate whether a Gram stain of endotracheal aspirates could be used to determine appropriate initial antimicrobial therapy for VAP. Data on consecutive episodes of microbiologically confirmed VAP were collected from February 2013 to February 2016 in the ICU of a tertiary care hospital in Japan. We constructed two hypothetical empirical antimicrobial treatment algorithms for VAP: a guidelines-based algorithm (GLBA) based on the recommendations of the American Thoracic Society-Infectious Diseases Society of America (ATS-IDSA) guidelines and a Gram stain-based algorithm (GSBA) which limited the choice of initial antimicrobials according to the results of bedside Gram stains. The GLBA and the GSBA were retrospectively reviewed for each VAP episode. The initial coverage rates and the selection of broad-spectrum antimicrobial agents were compared between the two algorithms. During the study period, 219 suspected VAP episodes were observed and 131 episodes were assessed for analysis. Appropriate antimicrobial coverage rates were not significantly different between the two algorithms (GLBA 95.4% versus GSBA 92.4%; p = 0.134). The number of episodes for which antimethicillin-resistant Staphylococcus aureus agents were selected as an initial treatment was larger in the GLBA than in the GSBA (71.0% versus 31.3%; p < 0.001), as were the number of episodes for which antipseudomonal agents were recommended as an initial treatment (70.2% versus 51.9%; p < 0.001). Antimicrobial treatment based on Gram stain results may restrict the administration of broad-spectrum antimicrobial agents without increasing the risk of treatment failure. UMIN-CTR, UMIN000026457 . Registered 8 March 2017 (retrospectively registered).

Evaluation of Machine Learning and Rules-Based Approaches for Predicting Antimicrobial Resistance Profiles in Gram-negative Bacilli from Whole Genome Sequence Data.

PubMed

Pesesky, Mitchell W; Hussain, Tahir; Wallace, Meghan; Patel, Sanket; Andleeb, Saadia; Burnham, Carey-Ann D; Dantas, Gautam

2016-01-01

The time-to-result for culture-based microorganism recovery and phenotypic antimicrobial susceptibility testing necessitates initial use of empiric (frequently broad-spectrum) antimicrobial therapy. If the empiric therapy is not optimal, this can lead to adverse patient outcomes and contribute to increasing antibiotic resistance in pathogens. New, more rapid technologies are emerging to meet this need. Many of these are based on identifying resistance genes, rather than directly assaying resistance phenotypes, and thus require interpretation to translate the genotype into treatment recommendations. These interpretations, like other parts of clinical diagnostic workflows, are likely to be increasingly automated in the future. We set out to evaluate the two major approaches that could be amenable to automation pipelines: rules-based methods and machine learning methods. The rules-based algorithm makes predictions based upon current, curated knowledge of Enterobacteriaceae resistance genes. The machine-learning algorithm predicts resistance and susceptibility based on a model built from a training set of variably resistant isolates. As our test set, we used whole genome sequence data from 78 clinical Enterobacteriaceae isolates, previously identified to represent a variety of phenotypes, from fully-susceptible to pan-resistant strains for the antibiotics tested. We tested three antibiotic resistance determinant databases for their utility in identifying the complete resistome for each isolate. The predictions of the rules-based and machine learning algorithms for these isolates were compared to results of phenotype-based diagnostics. The rules based and machine-learning predictions achieved agreement with standard-of-care phenotypic diagnostics of 89.0 and 90.3%, respectively, across twelve antibiotic agents from six major antibiotic classes. Several sources of disagreement between the algorithms were identified. Novel variants of known resistance factors and incomplete genome assembly confounded the rules-based algorithm, resulting in predictions based on gene family, rather than on knowledge of the specific variant found. Low-frequency resistance caused errors in the machine-learning algorithm because those genes were not seen or seen infrequently in the test set. We also identified an example of variability in the phenotype-based results that led to disagreement with both genotype-based methods. Genotype-based antimicrobial susceptibility testing shows great promise as a diagnostic tool, and we outline specific research goals to further refine this methodology.

Evaluation of anti-inflammatory and antimicrobial activity of AHPL/AYTOP/0213 cream

PubMed Central

Nipanikar, Sanjay U.; Nagore, Dheeraj; Chitlange, Soham S.; Buzruk, Devashree

2017-01-01

Background: Acne vulgaris is almost a widespread disease occurring in all races. Propionibacterium acnes initiate acne and inflammatory mediators aggravate it. Conventional therapies for acne include comedolytic, anti-inflammatory, and anti-biotic agents. Due to adverse effects of these therapies, people are searching for alternative options. In this context, a polyherbal formulation AHPL/AYTOP/0213 cream was developed for the treatment of Acne. Objective: The objective of this study is to study anti-inflammatory and antimicrobial activities of AHPL/AYTOP/0213 cream. Materials and Methods: Skin irritation study was conducted on AHPL/AYTOP/0213 cream as per OECD guidelines. (1) Anti-inflammatory activity: Anti-inflammatory activity of AHPL/AYTOP/0213 cream in comparison with diclofenac sodium cream was assessed in carrageenan-induced rat paw edema model. (2) Antimicrobial activity for P. acnes: P. acnes were incubated under anaerobic conditions. Aliquots of molten brain–heart infusion with glucose agar were used as the agar base. Formulation and clindamycin (10 mg/ml) were introduced in to the Agar wells randomly. (3) Antimicrobial activity for Staphylococcus epidermidis and Staphylococcus aureus: bacteria were incubated under aerobic conditions at 37°C. Tryptic soy broth with glucose agar was used as the agar base. A volume of 0.5 ml of formulation and clindamycin (10 mg/ml) were introduced in to the wells randomly. The antibacterial activity was evaluated by measuring zones of inhibition (in mm). Results: AHPL/AYTOP/0213 cream is nonirritant. Significant reduction in rat paw edema (43%) was observed with AHPL/AYTOP/0213 which was also comparable to diclofenac sodium cream (56.09%). Zone of inhibition for formulation was 20.68 mm, 28.20 mm, and 21.40 mm for P. acnes, S. epidermidis and S. aureus, respectively, which was comparable to clindamycin. The minimum inhibitory concentration of formulation AHPL/AYTOP/0213 obtained in anti-microbial study was 2.5 mg/mL. Conclusion: AHPL/AYTOP/0213 cream is nonirritant and possesses significant anti-inflammatory and antimicrobial activities, which further justifies its role in the management of acne vulgaris. PMID:29861599

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial.

PubMed

Bloos, Frank; Rüddel, Hendrik; Thomas-Rüddel, Daniel; Schwarzkopf, Daniel; Pausch, Christine; Harbarth, Stephan; Schreiber, Torsten; Gründling, Matthias; Marshall, John; Simon, Philipp; Levy, Mitchell M; Weiss, Manfred; Weyland, Andreas; Gerlach, Herwig; Schürholz, Tobias; Engel, Christoph; Matthäus-Krämer, Claudia; Scheer, Christian; Bach, Friedhelm; Riessen, Reimer; Poidinger, Bernhard; Dey, Karin; Weiler, Norbert; Meier-Hellmann, Andreas; Häberle, Helene H; Wöbker, Gabriele; Kaisers, Udo X; Reinhart, Konrad

2017-11-01

Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1-4.9 h) in the intervention group and 2.0 h (0.4-5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

Evaluation of early antimicrobial therapy adaptation guided by the BetaLACTA® test: a case-control study.

PubMed

Garnier, Marc; Rozencwajg, Sacha; Pham, Tài; Vimont, Sophie; Blayau, Clarisse; Hafiani, Mehdi; Fulgencio, Jean-Pierre; Bonnet, Francis; Mainardi, Jean-Luc; Arlet, Guillaume; Fartoukh, Muriel; Gallah, Salah; Quesnel, Christophe

2017-06-28

Rapid diagnostic tests detecting microbial resistance are needed for limiting the duration of inappropriateness of empirical antimicrobial therapy (EAT) in intensive care unit patients, besides reducing the use of broad-spectrum antibiotics. We hypothesized that the betaLACTA® test (BLT) could lead to early increase in the adequacy of antimicrobial therapy. This was a case-control study. Sixty-one patients with BLT-guided adaptation of EAT were prospectively included, and then matched with 61 "controls" having similar infection characteristics (community or hospital-acquired, and source of infection), in whom EAT was conventionally adapted to antibiogram results. Endpoints were to compare the proportion of appropriate (primary endpoint) and optimal (secondary endpoint) antimicrobial therapies with each of the two strategies, once microbiological sample culture results were available. Characteristics of patients, infections and EAT at inclusion were similar between groups. Nine early escalations of EAT occurred in the BLT-guided adaptation group, reaching 98% appropriateness vs. 77% in the conventional adaptation group (p < 0.01). The BLT reduced the time until escalation of an inappropriate EAT from 50.5 (48-73) to 27 (24-28) hours (p < 0.01). Seventeen early de-escalations occurred in the BLT-guided adaptation group, compared to one in the conventional adaptation group, reducing patients' exposure to broad-spectrum beta-lactam such as carbapenems. In multivariate analysis, use of the BLT was strongly associated with early appropriate (OR = 18 (3.4-333.8), p = 0.006) and optimal (OR = 35.5 (9.6-231.9), p < 0.001) antimicrobial therapies. Safety parameters were similar between groups. Our study suggests that a BLT-guided adaptation strategy may allow early beta-lactam adaptation from the first 24 hours following the beginning of sepsis management.

Antimicrobial photodynamic therapy combined with conventional endodontic treatment to eliminate root canal biofilm infection.

PubMed

Garcez, Aguinaldo S; Ribeiro, Martha S; Tegos, George P; Núñez, Silvia C; Jorge, Antonio O C; Hamblin, Michael R

2007-01-01

To compare the effectiveness of antimicrobial photodynamic therapy (PDT), standard endodontic treatment and the combined treatment to eliminate bacterial biofilms present in infected root canals. Ten single-rooted freshly extracted human teeth were inoculated with stable bioluminescent Gram-negative bacteria, Proteus mirabilis and Pseudomonas aeruginosa to form 3-day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify bacterial burdens. PDT employed a conjugate between polyethylenimine and chlorin(e6) as the photosensitizer (PS) and 660-nm diode laser light delivered into the root canal via a 200-micro fiber, and this was compared and combined with standard endodontic treatment using mechanical debridement and antiseptic irrigation. Endodontic therapy alone reduced bacterial bioluminescence by 90% while PDT alone reduced bioluminescence by 95%. The combination reduced bioluminescence by >98%, and importantly the bacterial regrowth observed 24 hours after treatment was much less for the combination (P<0.0005) than for either single treatment. Bioluminescence imaging is an efficient way to monitor endodontic therapy. Antimicrobial PDT may have a role to play in optimized endodontic therapy. (c) 2006 Wiley-Liss, Inc.

Management of aerobic vaginitis.

PubMed

Tempera, Gianna; Furneri, Pio Maria

2010-01-01

Aerobic vaginitis is a new nonclassifiable pathology that is neither specific vaginitis nor bacterial vaginosis. The diversity of this microbiological peculiarity could also explain several therapeutic failures when patients were treated for infections identified as bacterial vaginosis. The diagnosis 'aerobic vaginitis' is essentially based on microscopic examinations using a phase-contrast microscope (at ×400 magnification). The therapeutic choice for 'aerobic vaginitis' should take into consideration an antibiotic characterized by an intrinsic activity against the majority of bacteria of fecal origin, bactericidal effect and poor/absent interference with the vaginal microbiota. Regarding the therapy for aerobic vaginitis when antimicrobial agents are prescribed, not only the antimicrobial spectrum but also the presumed ecological disturbance on the anaerobic and aerobic vaginal and rectal microbiota should be taken into a consideration. Because of their very low impact on the vaginal microbiota, kanamycin or quinolones are to be considered a good choice for therapy. Copyright © 2010 S. Karger AG, Basel.

Antimicrobial photodynamic therapy for inactivation of biofilms formed by oral key pathogens

PubMed Central

Cieplik, Fabian; Tabenski, Laura; Buchalla, Wolfgang; Maisch, Tim

2014-01-01

With increasing numbers of antibiotic-resistant pathogens all over the world there is a pressing need for strategies that are capable of inactivating biofilm-state pathogens with less potential of developing resistances in pathogens. Antimicrobial strategies of that kind are especially needed in dentistry in order to avoid the usage of antibiotics for treatment of periodontal, endodontic or mucosal topical infections caused by bacterial or yeast biofilms. One possible option could be the antimicrobial photodynamic therapy (aPDT), whereby the lethal effect of aPDT is based on the principle that visible light activates a photosensitizer (PS), leading to the formation of reactive oxygen species, e.g., singlet oxygen, which induce phototoxicity immediately during illumination. Many compounds have been described as potential PS for aPDT against bacterial and yeast biofilms so far, but conflicting results have been reported. Therefore, the aim of the present review is to outline the actual state of the art regarding the potential of aPDT for inactivation of biofilms formed in vitro with a main focus on those formed by oral key pathogens and structured regarding the distinct types of PS. PMID:25161649

Determination of the Mutant Prevention Concentration and the Mutant Selection Window of Topical Antimicrobial Agents against Propionibacterium acnes.

PubMed

Nakase, Keisuke; Nakaminami, Hidemasa; Toda, Yuta; Noguchi, Norihisa

2017-01-01

Determination of the mutant prevention concentration (MPC) and the mutant selection window (MSW) of antimicrobial agents used to treat pathogenic bacteria is important in order to apply effective antimicrobial therapies. Here, we determined the MPCs of the major topical antimicrobial agents against Propionibacterium acnes and Staphylococcus aureus which cause skin infections and compared their MSWs. Among the MPCs of nadifloxacin and clindamycin, the clindamycin MPC was determined to be the lowest against P. acnes. In contrast, the nadifloxacin MPC was the lowest against S. aureus. Calculations based on the minimum inhibitory concentrations and MPCs showed that clindamycin has the lowest MSW against both P. acnes and S. aureus. Nadifloxacin MSWs were 4-fold higher against P. acnes than against S. aureus. It is more likely for P. acnes to acquire resistance to fluoroquinolones than S. aureus. Therefore, topical application of clindamycin contributes very little to the emergence of resistant P. acnes and S. aureus strains. © 2016 S. Karger AG, Basel.

The Antimicrobial Photodynamic Therapy in the Treatment of Peri-Implantitis

PubMed Central

Libotte, Fabrizio; Sabatini, Silvia; Grassi, Felice Roberto

2016-01-01

Introduction. The aim of this study is to demonstrate the effectiveness of addition of the antimicrobial photodynamic therapy to the conventional approach in the treatment of peri-implantitis. Materials and Methods. Forty patients were randomly assigned to test or control groups. Patients were assessed at baseline and at six (T1), twelve (T2), and twenty-four (T3) weeks recording plaque index (PlI), probing pocket depth (PPD), and bleeding on probing (BOP); control group received conventional periodontal therapy, while test group received photodynamic therapy in addition to it. Result. Test group showed a 70% reduction in the plaque index values and a 60% reduction in PD values compared to the baseline. BOP and suppuration were not detectable. Control group showed a significative reduction in plaque index and PD. Discussion. Laser therapy has some advantages in comparison to traditional therapy, with faster and greater healing of the wound. Conclusion. Test group showed after 24 weeks a better value in terms of PPD, BOP, and PlI, with an average pocket depth value of 2 mm, if compared with control group (3 mm). Our results suggest that antimicrobial photodynamic therapy with diode laser and phenothiazine chloride represents a reliable adjunctive treatment to conventional therapy. Photodynamic therapy should, however, be considered a coadjuvant in the treatment of peri-implantitis associated with mechanical (scaling) and surgical (grafts) treatments. PMID:27429618

Recombinant probiotics with antimicrobial peptides: a dual strategy to improve immune response in immunocompromised patients.

PubMed

Mandal, Santi M; Silva, Osmar N; Franco, Octavio L

2014-08-01

Bacterial infectious diseases are currently a serious health problem, especially in patients compromised by illness or those receiving immune-suppressant drugs. In this context, it is not only essential to improve the understanding of infectious mechanisms and host response but also to discover novel therapies with extreme urgency. Probiotics and antimicrobial peptides are also favorably viewed as novel strategies in the control of resistant bacteria. The present review will shed some light on the use of probiotic microorganisms expressing antimicrobial peptides as a dual therapy to control bacterial infectious diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Challenges and future in vaccines, drug development, and immunomodulatory therapy.

PubMed

Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L

2014-08-01

Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.

[Potential antimicrobial drug interactions in clinical practice: consequences of polypharmacy and multidrug resistance].

PubMed

Martínez-Múgica, Cristina

2015-12-01

Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the anti-infective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.

An evaluation of antimicrobial therapy for undifferentiated bovine respiratory disease

PubMed Central

Bateman, Ken G.; Martin, S. Wayne; Shewen, Patricia E.; Menzies, Paula I.

1990-01-01

A field trial of antimicrobial therapy for cases of undifferentiated bovine respiratory disease (UBRD) in beef calves was conducted at four Ontario feedlots. The primary purpose of the trial was to evaluate the efficacy of three different antimicrobials (oxytetracycline, penicillin, and trimethoprim-sulfadoxine) in the treatment of UBRD occurring within the first 28 days postarrival. The response, relapse, and case fatality rates overall were 85.7%, 14.8%, and 1.4%, respectively, and were not significantly different among the three antimicrobials evaluated. Weight gains of calves treated with the different drugs were not statistically different over the feeding period. Calves that suffered a relapse posttreatment were first treated significantly earlier (p<0.001) in the postarrival period than those that did not relapse. Considered together, treated calves gained significantly less (p<0.05) over the first 28 days and throughout the entire feeding period than controls that were never sick. Cases of UBRD that responded to therapy and did not relapse had rates of gain that were not significantly different from the controls. PMID:17423676

Effect of Two Cancer Chemotherapeutic Agents on the Antibacterial Activity of Three Antimicrobial Agents

PubMed Central

Moody, Marcia R.; Morris, Maureen J.; Young, Viola Mae; Moyé, Lemuel A.; Schimpff, Stephen C.; Wiernik, Peter H.

1978-01-01

Cancer chemotherapeutic agents and antibacterial antibiotics are often given concomitantly. Daunorubicin, cytosine arabinoside, and three antibiotics (gentamicin, amikacin, and ticarcillin) were tested individually and in combinations to determine their antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. These cytotoxic agents are commonly employed in the therapy of acute nonlymphocytic leukemia for remission induction therapy, and these antimicrobial agents are used in infection therapy. The maximum concentrations of the two cytotoxic drugs were chosen to be twice the known peak plasma levels of commonly employed dosage schedules. Neither of the cancer chemotherapeutic agents, alone or in combination, demonstrated bactericidal activity at the levels tested. However, in the presence of these agents, the antimicrobial activity of gentamicin and amikacin, although not that of ticarcillin, was depressed for 11 of 15 K. pneumoniae strains and 8 of 15 P. aeruginosa strains, but for none of the strains of E. coli. This level of decreased activity occasionally resulted in a minimal inhibitory concentration of the tested aminoglycoside well above the standard serum levels. Daunorubicin was more likely to antagonize gentamicin than was cytosine arabinoside. PMID:103494

Sepsis and Septic Shock Strategies.

PubMed

Armstrong, Bracken A; Betzold, Richard D; May, Addison K

2017-12-01

Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

National laboratory-based surveillance system for antimicrobial resistance: a successful tool to support the control of antimicrobial resistance in the Netherlands.

PubMed

Altorf-van der Kuil, Wieke; Schoffelen, Annelot F; de Greeff, Sabine C; Thijsen, Steven Ft; Alblas, H Jeroen; Notermans, Daan W; Vlek, Anne Lm; van der Sande, Marianne Ab; Leenstra, Tjalling

2017-11-01

An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the scientific impact and the possibility of detecting outbreaks may be amplified by merging the AMR surveillance database with databases from selected pathogen-based surveillance programmes containing patient data and genotypic typing data.

National laboratory-based surveillance system for antimicrobial resistance: a successful tool to support the control of antimicrobial resistance in the Netherlands

PubMed Central

Altorf-van der Kuil, Wieke; Schoffelen, Annelot F; de Greeff, Sabine C; Thijsen, Steven FT; Alblas, H Jeroen; Notermans, Daan W; Vlek, Anne LM; van der Sande, Marianne AB; Leenstra, Tjalling

2017-01-01

An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the scientific impact and the possibility of detecting outbreaks may be amplified by merging the AMR surveillance database with databases from selected pathogen-based surveillance programmes containing patient data and genotypic typing data. PMID:29162208

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2015-03-01

antimicrobials (and antiseptics) as well as to evaluate the effectiveness of various biofilm dispersal agents utilizing a number of bacterial species as...combat related wounds. 3 Demonstrated the utility of combinations of biofilm dispersal agents and antimicrobials as an alternate therapy for...alone or in combination with antimicrobials ) to reduce infection in contaminated femoral segmental defects. 5 Characterized host responses of

Influence of antibiotic-regimens on intensive-care unit-mortality and liver-cirrhosis as risk factor.

PubMed

Friedrich-Rust, Mireen; Wanger, Beate; Heupel, Florian; Filmann, Natalie; Brodt, Reinhard; Kempf, Volkhard Aj; Kessel, Johanna; Wichelhaus, Thomas A; Herrmann, Eva; Zeuzem, Stefan; Bojunga, Joerg

2016-04-28

To assess the rate of infection, appropriateness of antimicrobial-therapy and mortality on intensive care unit (ICU). Special focus was drawn on patients with liver cirrhosis. The study was approved by the local ethical committee. All patients admitted to the Internal Medicine-ICU between April 1, 2007 and December 31, 2009 were included. Data were extracted retrospectively from all patients using patient charts and electronic documentations on infection, microbiological laboratory reports, diagnosis and therapy. Due to the large hepatology department and liver transplantation center, special interest was on the subgroup of patients with liver cirrhosis. The primary statistical-endpoint was the evaluation of the influence of appropriate versus inappropriate antimicrobial-therapy on in-hospital-mortality. Charts of 1979 patients were available. The overall infection-rate was 53%. Multiresistant-bacteria were present in 23% of patients with infection and were associated with increased mortality (P < 0.000001). Patients with infection had significantly increased in-hospital-mortality (34% vs 17%, P < 0.000001). Only 9% of patients with infection received inappropriate initial antimicrobial-therapy, no influence on mortality was observed. Independent risk-factors for in-hospital-mortality were the presence of septic-shock, prior chemotherapy for malignoma and infection with Pseudomonas spp. Infection and mortality-rate among 175 patients with liver-cirrhosis was significantly higher than in patients without liver-cirrhosis. Infection increased mortality 2.24-fold in patients with cirrhosis. Patients with liver cirrhosis were at an increased risk to receive inappropriate initial antimicrobial therapy. The results of the present study report the successful implementation of early-goal-directed therapy. Liver cirrhosis patients are at increased risk of infection, mortality and to receive inappropriate therapy. Increasing burden are multiresistant-bacteria.

Study results on the use of different therapies for the treatment of vaginitis in hospitalised pregnant women.

PubMed

Novakov Mikić, Aleksandra; Stojic, Sinisa

2015-08-01

During pregnancy, many women experience vaginal infections due to a weakened immune system and changes in hormonal status. Treating these infections is of crucial importance, because women are at high risk for serious complications such as preterm birth and late miscarriage. For this reason, the present study was conducted to investigate the effectiveness of octenidine dihydrochloride/phenoxyethanol (OHP) in comparison to antimicrobial therapies in pregnant women in hospital suffering from different types of vaginitis. A total of 1,000 patients were divided into 4 different groups according to their type of vaginal infection after smear analyses. Each group was again divided into two subgroups receiving treatment with OHP or antimicrobial therapies with neomycin/polymyxin B/nystatin, metronidazole or miconazole vaginal tablets. The most frequent causes of vaginitis were unspecific bacterial infections (42.4 %) and vaginal candidiasis (44.8 %). The average time needed to obtain negative results from smear analyses was significantly shorter when treated with OHP, both in patients with bacterial vaginosis (BV) or vaginal candidiasis (VC) compared to antimicrobial therapy (1.7 ± 0.8 vs. 2.3 ± 1.1 days; 2.3 ± 1.4 vs. 3.4 ± 1.6 days; both p < 0.001). Equally, the maximum number of days until negative results were detected was significantly lower with OHP compared to antimicrobial therapy (BV: 3 vs. 5 days; VC: 5 vs. 7 days). OHP has a great effect in the treatment of vaginitis during pregnancy and thus should be an integral part of standard therapy regimens.

C. albicans Growth, Transition, Biofilm Formation, and Gene Expression Modulation by Antimicrobial Decapeptide KSL-W

DTIC Science & Technology

2013-11-07

Simon Theberge1, Abdelhabib Semlali1,2, Abdullah Alamri1, Kai P Leung3 and Mahmoud Rouabhia1* Abstract Background: Antimicrobial peptides have been the... peptides , including KSL-W (KKVVFWVKFK-NH2), for potential clinical use. Because this peptide displays antimicrobial activity against bacteria, we sought...the efficacy of KSL-W against C. albicans and its potential use as an antifungal therapy. Keywords: Antimicrobial peptide , KSL-W, C. albicans, Growth

Local and systemic antimicrobial therapy in periodontics.

PubMed

Herrera, David; Matesanz, Paula; Bascones-Martínez, Antonio; Sanz, Mariano

2012-09-01

This review aimed to update the current evidence on the efficacy of the adjunctive use of local and systemic antimicrobials in the treatment of periodontitis and to assess whether it might improve the clinical limitations and shortcomings of standard nonsurgical treatment in the management of periodontitis. Relevant randomized clinical trials (RCT) with more than 3 months of follow-up, published from 2010 to 2012 for systemic antimicrobials and from 2008 to 2012 for local antimicrobials, were searched in Medline and critically analyzed. Scientific evidence evaluated in different systematic reviews and reviews presented at European and World Workshops were also included. Only adjunctive therapies were considered in the present review: articles comparing debridement alone or plus placebo, versus debridement plus systemic or local antimicrobials were included. Adjunctive systemic antimicrobials have been evaluated both in aggressive and chronic periodontitis: in aggressive periodontitis, amoxicillin and metronidazole have been extensively studied, reporting clinical and microbiological benefits; in chronic periodontitis, different products are under scrutiny, such as azithromycin. The clinical efficacy of local antimicrobials, although extensively demonstrated, is still surrounded by a constant debate on the cost-effectiveness evaluation and on its adequate indications. Despite the clinical efficacy of the adjunctive use of local and systemic antimicrobials, demonstrated in RCTs and in systematic reviews, there is a lack of evidence to support well-defined clinical protocols, including products and dosages. Copyright © 2012 Elsevier Inc. All rights reserved.

Antimicrobial stewardship programs: how to start and steer a successful program.

PubMed

Drew, Richard H

2009-03-01

Antimicrobial stewardship programs (ASPs) promote the appropriate use of antimicrobials by selecting the appropriate dose, duration, and route of administration. The appropriate use of antimicrobials has the potential to improve efficacy, reduce treatment-related costs, minimize drug-related adverse events, and limit the potential for emergence of antimicrobial resistance. To summarize ASP tactics that can improve the appropriate use of antimicrobials in the hospital setting. Several measures can be used to implement such programs and gain multidisciplinary support while addressing common barriers. Implementation of an ASP requires a multidisciplinary approach with an infectious diseases physician and a clinical pharmacist with infectious diseases training as its core team members. As identified by recently published guidelines, 2 proactive strategies for promoting antimicrobial stewardship include: (1) formulary restriction and pre-authorization, and (2) prospective audit with intervention and feedback. Other supplemental strategies involve education, guidelines and clinical pathways, antimicrobial order forms, de-escalation of therapy, intravenous-to-oral (IV-to-PO) switch therapy, and dose optimization. Several barriers exist to successful implementation of ASPs. These include obtaining adequate administrative support and compensation for team members. Gaining physician acceptance can also be challenging if there is a perceived loss of autonomy in clinical decision making. ASPs have the potential to reduce antimicrobial resistance, health care costs, and drug-related adverse events while improving clinical outcomes. The efforts and expense required to implement and maintain ASPs are more than justified given their potential benefits to both the hospital and the patient.

The history of gold therapy for tuberculosis.

PubMed

Benedek, Thomas G

2004-01-01

This is a historical study of the popularization of a medical therapy contrary to pertinent experimental findings. Presumably this circumstance reflects the desperation about tuberculosis: highly prevalent, highly fatal, and lacking any etiologically directed therapy. Gold compounds were introduced, based initially on the reputation of Robert Koch, who had found gold cyanide effective against M. tuberculosis in cultures, but not in experimentally infected animals. Treatment of pulmonary tuberculosis with these compounds was popularized, particularly by Danish physicians, in the mid-1920s, despite consistently negative experimental results, based on Paul Ehrlich's theories of antimicrobial drug effects. Difficulties in the design of interpretable clinical studies were soon recognized but also generally ignored, thus permitting data to be interpreted as favorable to antituberculous gold therapy. Eventually toxicity was considered to outweigh the alleged therapeutic benefit of all gold compounds. This resulted in their discard shortly before the introduction of streptomycin therapy.

Antimicrobial multidrug resistance and coresistance patterns of Mannheimia haemolytica isolated from bovine respiratory disease cases--a three-year (2009-2011) retrospective analysis.

PubMed

Lubbers, Brian V; Hanzlicek, Gregg A

2013-05-01

Bovine respiratory disease continues to be the most important ailment of feed yard cattle. While the disease is multifactorial in nature, therapy continues to target the primary bacterial pathogens, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. A survey of records from a single diagnostic laboratory was conducted to evaluate the percentage of M. haemolytica isolates that were resistant to multiple antimicrobials and if coresistance patterns could be detected. All susceptibility test results for M. haemolytica recovered from lung tissues of cattle were eligible for inclusion in the survey. There were no isolates over the course of the analysis that were resistant to all 6 antimicrobials, primarily due to a lack of resistance to ceftiofur. In 2009, just over 5% of isolates were resistant to 5 or more antimicrobials (pan-resistant). In 2011, more than 35% of the M. haemolytica isolates were characterized as pan-resistant. Significant antimicrobial coresistance patterns were only seen with oxytetracycline and tilmicosin; bacterial isolates that were resistant to either oxytetracycline or tilmicosin were more likely to be resistant to at least one other antimicrobial. The mechanisms by which M. haemolytica is developing multidrug resistance warrant investigation if antimicrobial utility in the therapy of bovine respiratory disease is to be preserved.

[The interplay of diagnostic and antimicrobial stewardship for the management of septic patients: the Tuscan model.

PubMed

Forni, Silvia; Toccafondi, Giulio; Viaggi, Bruno; Grazzini, Maddalena; D'Arienzo, Sara; Gemmi, Fabrizio; Vannucci, Andrea; Tulli, Giorgio

2018-02-01

Antimicrobial resistance is a global threat caused by the rapid spread of multiresistant microorganisms. Antimicrobial stewardship (AS) is a coordinated intervention designed to improve the appropriate use of antimicrobials by promoting the selection of the optimal drug regimen, dose, duration of therapy and route of administration. AS programs have proved effective in reducing antimicrobial resistance, inappropriate antimicrobial use and in improving patient outcomes. Recently developed rapid diagnostic technologies in microbiology (RDTM) allows a faster and etiological diagnosis of infection and a reduction in the use of unnecessary empirical therapies. This may result in important advancement in time-critical care pathways for septic patients. Nevertheless, RDTM are costly and if not rationally positioned may consume resources and hinder the efficacy of AS programs. In this regard, Tuscany Region is engaged in designing, through a systemic approach, an effective high-quality clinical microbiological service grid. In order to develop a sustainable and equitable model for integrating diagnostic and antimicrobial stewardship we conducted a survey in the regional network of 14 microbiological laboratories. The results shows that in order to develop a sustainable service we need to improve the communication at the interface between laboratories and care unit, harmonize the time windows for processing samples and to devise a robust score for stratifying patient with suspected sepsis.

Microbial etiology of febrile neutropenia.

PubMed

Swati, Mudshingkar; Gita, Nataraj; Sujata, Baveja; Farah, Jijina; Preeti, Mehta

2010-06-01

Bacterial and fungal infections are a major cause of morbidity and mortality among neutropenic patients. The choice of empiric antimicrobial regimen is based on susceptibility pattern of locally prevalent pathogens. From 64 febrile neutropenic patients with clinical sepsis, blood and other appropriate clinical specimens were processed to determine bacterial and fungal spectrum and their antimicrobial susceptibility pattern. Risk factors for developing sepsis were determined by case-control study. 68 organisms were recovered. Fifteen (22.05%) were Gram-positive cocci with predominance of methicillin Sensitive S. aureus (10.29%), 47 (69.11%) were Gram-negative rods with predominance of Klebsiella pneumoniae (30.88%) and four were Non albicans Candida. 81% and 60% of Klebsiella and E. coli were ESBL producers. All species of Candida were sensitive to amphoterecin B and voriconazole. Duration and extent of neutropenia, chemotherapy, immunosuppressive therapy, altered mucosal barriers and presence of central venous lines were statistically significant risk factors for developing sepsis. Gram-negative bacteria were the predominant isolates. The choice of therapy in neutropenic patients should be formulated based on local spectrum of microbes and local and regional resistance patterns.

Microbial Etiology of Febrile Neutropenia

PubMed Central

Gita, Nataraj; Sujata, Baveja; Farah, Jijina; Preeti, Mehta

2010-01-01

Bacterial and fungal infections are a major cause of morbidity and mortality among neutropenic patients. The choice of empiric antimicrobial regimen is based on susceptibility pattern of locally prevalent pathogens. From 64 febrile neutropenic patients with clinical sepsis, blood and other appropriate clinical specimens were processed to determine bacterial and fungal spectrum and their antimicrobial susceptibility pattern. Risk factors for developing sepsis were determined by case–control study. 68 organisms were recovered. Fifteen (22.05%) were Gram-positive cocci with predominance of methicillin Sensitive S. aureus (10.29%), 47 (69.11%) were Gram-negative rods with predominance of Klebsiella pneumoniae (30.88%) and four were Non albicans Candida. 81% and 60% of Klebsiella and E. coli were ESBL producers. All species of Candida were sensitive to amphoterecin B and voriconazole. Duration and extent of neutropenia, chemotherapy, immunosuppressive therapy, altered mucosal barriers and presence of central venous lines were statistically significant risk factors for developing sepsis. Gram-negative bacteria were the predominant isolates. The choice of therapy in neutropenic patients should be formulated based on local spectrum of microbes and local and regional resistance patterns. PMID:21629636

Risk factors and therapy for goat mastitis in a hospital-based case-control study in Bangladesh.

PubMed

Koop, Gerrit; Islam, Md Nurul; Rahman, Md Mizanur; Khatun, Momena; Ferdous, Jinnat; Sayeed, Md Abu; Islam, Shariful; Ahaduzzaman, Md; Akter, Sazeda; Mannan, Abdul; Hassan, Mohammad Mahmudul; Dissanayake, Ravi; Hoque, Md Ahasanul

2016-02-01

Bangladesh has a large population of goats, which contribute to the income, nutrition and welfare of the households of many families. Mastitis in goats has a low incidence, but is often very severe, making veterinary care necessary. The aim of this study was to identify seasonality and risk factors for goat mastitis in a hospital-based matched case-control study in a teaching veterinary hospital in Chittagong, Bangladesh and to describe the range of antimicrobial treatments applied in this situation. Cases of mastitis and controls were drawn from the hospital patient recording system, along with their risk factor status. Multiple imputation was applied to deal with the missing values in the data analysis. Mastitis occurred somewhat more in the rainy season, and comprised about 3% of all goats admitted to the hospital during January 2011-June 2014. Free-ranging farming system, poor body condition score and non-native goat breeds were significantly associated with case status. Treatment of clinical mastitis was variable and unsystematic, but the use of gentamicin was commonly recorded. The need for more prudent and evidence-based antimicrobial therapies is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Public health risk of antimicrobial resistance transfer from companion animals.

PubMed

Pomba, Constança; Rantala, Merja; Greko, Christina; Baptiste, Keith Edward; Catry, Boudewijn; van Duijkeren, Engeline; Mateus, Ana; Moreno, Miguel A; Pyörälä, Satu; Ružauskas, Modestas; Sanders, Pascal; Teale, Christopher; Threlfall, E John; Kunsagi, Zoltan; Torren-Edo, Jordi; Jukes, Helen; Törneke, Karolina

2017-04-01

Antimicrobials are important tools for the therapy of infectious bacterial diseases in companion animals. Loss of efficacy of antimicrobial substances can seriously compromise animal health and welfare. A need for the development of new antimicrobials for the therapy of multiresistant infections, particularly those caused by Gram-negative bacteria, has been acknowledged in human medicine and a future corresponding need in veterinary medicine is expected. A unique aspect related to antimicrobial resistance and risk of resistance transfer in companion animals is their close contact with humans. This creates opportunities for interspecies transmission of resistant bacteria. Yet, the current knowledge of this field is limited and no risk assessment is performed when approving new veterinary antimicrobials. The objective of this review is to summarize the current knowledge on the use and indications for antimicrobials in companion animals, drug-resistant bacteria of concern among companion animals, risk factors for colonization of companion animals with resistant bacteria and transmission of antimicrobial resistance (bacteria and/or resistance determinants) between animals and humans. The major antimicrobial resistance microbiological hazards originating from companion animals that directly or indirectly may cause adverse health effects in humans are MRSA, methicillin-resistant Staphylococcus pseudintermedius, VRE, ESBL- or carbapenemase-producing Enterobacteriaceae and Gram-negative bacteria. In the face of the previously recognized microbiological hazards, a risk assessment tool could be applied in applications for marketing authorization for medicinal products for companion animals. This would allow the approval of new veterinary medicinal antimicrobials for which risk levels are estimated as acceptable for public health. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

PubMed

Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

2017-01-01

Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Expert Consensus on Metrics to Assess the Impact of Patient-Level Antimicrobial Stewardship Interventions in Acute-Care Settings

PubMed Central

Anderson, Deverick J.; Cochran, Ronda L.; Hicks, Lauri A.; Srinivasan, Arjun; Dodds Ashley, Elizabeth S.

2017-01-01

Antimicrobial stewardship programs (ASPs) positively impact patient care, but metrics to assess ASP impact are poorly defined. We used a modified Delphi approach to select relevant metrics for assessing patient-level interventions in acute-care settings for the purposes of internal program decision making. An expert panel rated 90 candidate metrics on a 9-point Likert scale for association with 4 criteria: improved antimicrobial prescribing, improved patient care, utility in targeting stewardship efforts, and feasibility in hospitals with electronic health records. Experts further refined, added, or removed metrics during structured teleconferences and re-rated the retained metrics. Six metrics were rated >6 in all criteria: 2 measures of Clostridium difficile incidence, incidence of drug-resistant pathogens, days of therapy over admissions, days of therapy over patient days, and redundant therapy events. Fourteen metrics rated >6 in all criteria except feasibility were identified as targets for future development. PMID:27927866

Whole-Genome Sequencing for Detecting Antimicrobial Resistance in Nontyphoidal Salmonella.

PubMed

McDermott, Patrick F; Tyson, Gregory H; Kabera, Claudine; Chen, Yuansha; Li, Cong; Folster, Jason P; Ayers, Sherry L; Lam, Claudia; Tate, Heather P; Zhao, Shaohua

2016-09-01

Laboratory-based in vitro antimicrobial susceptibility testing is the foundation for guiding anti-infective therapy and monitoring antimicrobial resistance trends. We used whole-genome sequencing (WGS) technology to identify known antimicrobial resistance determinants among strains of nontyphoidal Salmonella and correlated these with susceptibility phenotypes to evaluate the utility of WGS for antimicrobial resistance surveillance. Six hundred forty Salmonella of 43 different serotypes were selected from among retail meat and human clinical isolates that were tested for susceptibility to 14 antimicrobials using broth microdilution. The MIC for each drug was used to categorize isolates as susceptible or resistant based on Clinical and Laboratory Standards Institute clinical breakpoints or National Antimicrobial Resistance Monitoring System (NARMS) consensus interpretive criteria. Each isolate was subjected to whole-genome shotgun sequencing, and resistance genes were identified from assembled sequences. A total of 65 unique resistance genes, plus mutations in two structural resistance loci, were identified. There were more unique resistance genes (n = 59) in the 104 human isolates than in the 536 retail meat isolates (n = 36). Overall, resistance genotypes and phenotypes correlated in 99.0% of cases. Correlations approached 100% for most classes of antibiotics but were lower for aminoglycosides and beta-lactams. We report the first finding of extended-spectrum β-lactamases (ESBLs) (blaCTX-M1 and blaSHV2a) in retail meat isolates of Salmonella in the United States. Whole-genome sequencing is an effective tool for predicting antibiotic resistance in nontyphoidal Salmonella, although the use of more appropriate surveillance breakpoints and increased knowledge of new resistance alleles will further improve correlations. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group.

PubMed

Kimura, Shun-Ichi; Fujita, Hiroyuki; Kato, Hideaki; Hiramoto, Nobuhiro; Hosono, Naoko; Takahashi, Tsutomu; Shigeno, Kazuyuki; Hatsumi, Naoko; Minamiguchi, Hitoshi; Miyatake, Junichi; Handa, Hiroshi; Akiyama, Nobu; Kanda, Yoshinobu; Yoshida, Minoru; Kiyoi, Hitoshi; Miyazaki, Yasushi; Naoe, Tomoki

2017-11-01

We performed a nationwide questionnaire-based survey to evaluate the current clinical practices of infectious complications during chemotherapy for acute leukemia in Japan. We e-mailed a questionnaire to member institutions of the Japan Adult Leukemia Study Group in September, 2013. The questionnaire consisted of 50 multiple-choice questions covering therapeutic environment, antimicrobial prophylaxis, screening test during neutropenia, empirical therapy for febrile neutropenia, and the use of granulocyte-colony stimulating factor. The results were compared to those of previous surveys conducted in 2001 and 2007, and also to the recommendations described in the guidelines. Usable responses were received from 141 out of 222 (63.5%) institutions. Chemotherapy for acute myeloid leukemia was performed in protective environment in 90% of the institutions, which increased compared to previous survey (76%). Fluoroquinolones and fluconazole were the most commonly used antimicrobial agents for antibacterial and antifungal prophylaxis, followed by sulfamethoxazole-trimethoprim and itraconazole, respectively. In empirical therapy for febrile neutropenia, monotherapy with β-lactum antibiotics was the first-line therapy in most of the institutions. While empirical antifungal therapy was adopted for persistent fever in more than half of the institutions, preemptive/presumptive therapy was also used in approximately 40% of the institutions. Most of the clinicians were reluctant to use granulocyte-colony stimulating factor routinely in chemotherapy for acute myeloid leukemia. This study clarified the current clinical practices of infectious complications during chemotherapy for acute leukemia and would provide important information for the development of a suitable guideline in Japan.

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2015-03-01

antimicrobials (and antiseptics) as well as to evaluate the effectiveness of various biofilm dispersal agents utilizing a number of bacterial species as well...combat related wounds. 3 Demonstrated the utility of combinations of biofilm dispersal agents and antimicrobials as an alternate therapy for targeting...alone or in combination with antimicrobials ) to reduce infection in contaminated femoral segmental defects. 5 Characterized host responses of

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2015-05-01

2011-9/6/2014 1 Developed in vitrobiofilm assays to test susceptibility to various antimicrobials (and antiseptics) as well as to evaluate the...combinations of biofilm dispersal agents and antimicrobials as an alternate therapy for targeting bacterial biofilms. 4 Through collaborative efforts...contributed to the development of biomaterials capable of delivering biofilm dispersal agents (alone or in combination with antimicrobials ) to reduce

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2015-04-01

Sanchez, Carlos 9/7/2011-9/6/2014 1 Developed in vitrobiofilm assays to test susceptibility to various antimicrobials (and antiseptics) as well as to...utility of combinations of biofilm dispersal agents and antimicrobials as an alternate therapy for targeting bacterial biofilms. 4 Through...collaborative efforts contributed to the development of biomaterials capable of delivering biofilm dispersal agents (alone or in combination with antimicrobials

Antimicrobial resistance in Escherichia coli O157 and non-O157 isolated from feces of domestic farm animals in Culiacan, Mexico

USDA-ARS?s Scientific Manuscript database

Antimicrobial resistance in E. coli O157 and non-O157 strains is a matter of increasing concern, and the association with some virulence traits in the same bacteria remains unclear. Inappropriate antimicrobial use in human and animal therapy has been associated with selective pressure in enteric mi...

Antimicrobial resistance in Escherichia coli O157 and non-O157 recovered from feces of domestic farm animals in Northwestern Mexico

USDA-ARS?s Scientific Manuscript database

Antimicrobial resistance in Shiga toxin-producing Escherichia coli (STEC) O157 and non-O157 is a matter of increasing concern. Inappropriate antimicrobial use in human and animal therapy has been associated with an acquired resistance in enteric microorganisms. The aim of the present study was to de...

Molecular Detection of Antimicrobial Resistance

PubMed Central

Fluit, Ad C.; Visser, Maarten R.; Schmitz, Franz-Josef

2001-01-01

The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. PMID:11585788

Antimicrobial Photodynamic Therapy and Dental Plaque: A Systematic Review of the Literature

PubMed Central

Santin, G. C.; Oliveira, D. S. B.; Galo, R.; Borsatto, M. C.; Corona, S. A. M.

2014-01-01

Background. The aim of this study was to perform a systematic review of the literature on the efficacy of antimicrobial photodynamic therapy (PDTa) on cariogenic dental biofilm. Types of Studies Reviewed. Studies in vivo, in vitro, and in situ were included. Articles that did not address PDTa, those that did not involve cariogenic biofilm, those that used microorganisms in the plankton phase, and reviews were excluded. Data extraction and quality assessments were performed independently by two raters using a scale. Results. Two hundred forty articles were retrieved; only seventeen of them met the eligibility criteria and were analyzed in the present review. Considerable variability was found regarding the methodologies and application protocols for antimicrobial PDTa. Two articles reported unfavorable results. Practical Implications. The present systematic review does not allow drawing any concrete conclusions regarding the efficacy of antimicrobial PDTa, although this method seems to be a promising option. PMID:25379545

Treatment practices and quantification of antimicrobial drug usage in conventional and organic dairy farms in Wisconsin.

PubMed

Pol, M; Ruegg, P L

2007-01-01

The objective of this study was to develop a method to quantify antimicrobial drug usage and treatment practices on conventional and organic dairy farms that had been recruited to represent a broad spectrum of potential exposure to antimicrobial drugs. Data on disease prevalence and treatment practices of organic (n = 20) and conventional (n = 20) farms were obtained during a farm visit using a survey instrument. A standardized estimate of antimicrobial drug usage was developed using a defined daily dose (DDD) of selected compounds. Density of antimicrobial drug usage was expressed as the number of DDD per adult cow per year. Differences in prevalence and management of selected diseases between conventional and organic farms were identified. The overall estimated prevalence of selected diseases was greater for conventional farms compared with organic farms. Organic farmers reported use of a variety of nonantimicrobial compounds for treatment and prevention of disease. Conventional farmers reported that penicillin was the compound most commonly used for dry cow therapy and cephapirin was most commonly used for treatment of clinical mastitis. On conventional farms, the estimated overall exposure to antimicrobial drugs was 5.43 DDD per cow per year composed of 3.58 and 1.85 DDD of intramammary and parenteral antimicrobial drugs, respectively. Of total intramammary antimicrobial drug usage, treatment of clinical mastitis contributed 2.02 DDD compared with 1.56 DDD attributed to the use of dry cow therapy. Of total parenteral treatments, the distribution of exposure was 0.52 (dry cow therapy), 1.43 (clinical mastitis treatment), 0.39 (treatment of foot disease), 0.14 (treatment of respiratory disease), and 0.32 (treatment of metritis) DDD. For treatments of foot infections (0.33 DDD), respiratory infections (0.07 DDD), and metritis (0.19 DDD), the mean density of ceftiofur usage was significantly greater compared with other compounds.

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

PubMed Central

Cosgrove, Sara E.; Maragakis, Lisa L.

2012-01-01

Summary: Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria. PMID:22763634

In vitro bacterial isolate susceptibility to empirically selected antimicrobials in 111 dogs with bacterial pneumonia.

PubMed

Proulx, Alexandre; Hume, Daniel Z; Drobatz, Kenneth J; Reineke, Erica L

2014-01-01

To determine the proportion of airway bacterial isolates resistant to both empirically selected and recently administered antimicrobials, and to assess the impact of inappropriate initial empiric antimicrobials selection on length of hospital stay and survival to discharge in dogs with bacterial pneumonia. Retrospective study. University veterinary teaching hospital. One hundred and eleven dogs with a clinical diagnosis of bacterial pneumonia that had aerobic bacterial culture and susceptibility testing performed from a tracheal wash sample. None. Overall, 26% (29/111) of the dogs had at least 1 bacterial isolate that was resistant to empirically selected antimicrobials. In dogs with a history of antimicrobial administration within the preceding 4 weeks, a high incidence (57.4%, 31/54) of in vitro bacterial resistance to those antimicrobials was found: 64.7% (11/17) in the community-acquired pneumonia group, 55.2% (16/29) in the aspiration pneumonia group, and 50.0% (4/8) in the other causes of bacterial pneumonia group. No statistically significant association was found between bacterial isolate resistance to empirically selected antimicrobials and length of hospital stay or mortality. The high proportion of in vitro airway bacterial resistance to empiric antimicrobials would suggest that airway sampling for bacterial culture and susceptibility testing may be helpful in guiding antimicrobial therapy and recently administered antimicrobials should be avoided when empirically selecting antimicrobials. Although no relationship was found between inappropriate initial empiric antimicrobial selection and length of hospital stay or mortality, future prospective studies using standardized airway-sampling techniques, treatment modalities, and stratification of disease severity based on objective values, such as arterial blood gas analysis in all dogs with pneumonia, would be needed to determine if a clinical effect of in vitro bacterial resistance to empirically administered antimicrobials truly exists or not. © Veterinary Emergency and Critical Care Society 2013.

Biofilm disruption with rotating microrods enhances antimicrobial efficacy

NASA Astrophysics Data System (ADS)

Mair, Lamar O.; Nacev, Aleksandar; Hilaman, Ryan; Stepanov, Pavel Y.; Chowdhury, Sagar; Jafari, Sahar; Hausfeld, Jeffrey; Karlsson, Amy J.; Shirtliff, Mark E.; Shapiro, Benjamin; Weinberg, Irving N.

2017-04-01

Biofilms are a common and persistent cause of numerous illnesses. Compared to planktonic microbes, biofilm residing cells often demonstrate significant resistance to antimicrobial agents. Thus, methods for dislodging cells from the biofilm may increase the antimicrobial susceptibility of such cells, and serve as a mechanical means of increasing antimicrobial efficacy. Using Aspergillus fumigatus as a model microbe, we magnetically rotate microrods in and around biofilm. We show that such rods can improve the efficacy of antimicrobial Amphotericin B treatments in vitro. This work represents a first step in using kinetic magnetic particle therapy for disrupting fungal biofilms.

Clinical outcome comparison of immediate blanket treatment versus a delayed pathogen-based treatment protocol for clinical mastitis in a New York dairy herd.

PubMed

Vasquez, A K; Nydam, D V; Capel, M B; Eicker, S; Virkler, P D

2017-04-01

The purpose was to compare immediate intramammary antimicrobial treatment of all cases of clinical mastitis with a selective treatment protocol based on 24-h culture results. The study was conducted at a 3,500-cow commercial farm in New York. Using a randomized design, mild to moderate clinical mastitis cases were assigned to either the blanket therapy or pathogen-based therapy group. Cows in the blanket therapy group received immediate on-label intramammary treatment with ceftiofur hydrochloride for 5 d. Upon receipt of 24 h culture results, cows in the pathogen-based group followed a protocol automatically assigned via Dairy Comp 305 (Valley Agricultural Software, Tulare, CA): Staphylococcus spp., Streptococcus spp., or Enterococcus spp. were administered on-label intramammary treatment with cephapirin sodium for 1 d. Others, including cows with no-growth or gram-negative results, received no treatment. A total of 725 cases of clinical mastitis were observed; 114 cows were not enrolled due to severity. An additional 122 cases did not meet inclusion criteria. Distribution of treatments for the 489 qualifying events was equal between groups (pathogen-based, n = 246; blanket, n = 243). The proportions of cases assigned to the blanket and pathogen-based groups that received intramammary therapy were 100 and 32%, respectively. No significant differences existed between blanket therapy and pathogen-based therapy in days to clinical cure; means were 4.8 and 4.5 d, respectively. The difference in post-event milk production between groups was not statistically significant (blanket therapy = 34.7 kg; pathogen-based = 35.4 kg). No differences were observed in test-day linear scores between groups; least squares means of linear scores was 4.3 for pathogen-based cows and 4.2 for blanket therapy cows. Odds of survival 30 d postenrollment was similar between groups (odds ratio of pathogen-based = 1.6; 95% confidence interval: 0.7-3.7) as was odds of survival to 60 d (odds ratio = 1.4; 95% confidence interval: 0.7-2.6). The one significant difference found for the effect of treatment was in hospital days; pathogen-based cows experienced, on average, 3 fewer days than blanket therapy cows. A majority (68.5%) of moderate and mild clinical cases would not have been treated if all cows on this trial were enrolled in a pathogen-based protocol. The use of a strategic treatment protocol based on 24-h postmastitis pathogen results has potential to efficiently reduce antimicrobial use. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Antimicrobial Photodynamic Therapy Combined With Conventional Endodontic Treatment to Eliminate Root Canal Biofilm Infection

PubMed Central

Garcez, Aguinaldo S.; Ribeiro, Martha S.; Tegos, George P.; Núñez, Silvia C.; Jorge, Antonio O.C.; Hamblin, Michael R.

2011-01-01

Background and Objective To compare the effectiveness of antimicrobial photodynamic therapy (PDT), standard endodontic treatment and the combined treatment to eliminate bacterial biofilms present in infected root canals. Study Design/Materials and Methods Ten single-rooted freshly extracted human teeth were inoculated with stable bioluminescent Gram-negative bacteria, Proteus mirabilis and Pseudomonas aeruginosa to form 3-day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify bacterial burdens. PDT employed a conjugate between polyethylenimine and chlorin(e6) as the photosensitizer (PS) and 660-nm diode laser light delivered into the root canal via a 200-µ fiber, and this was compared and combined with standard endodontic treatment using mechanical debridement and antiseptic irrigation. Results Endodontic therapy alone reduced bacterial bioluminescence by 90% while PDT alone reduced bioluminescence by 95%. The combination reduced bioluminescence by >98%, and importantly the bacterial regrowth observed 24 hours after treatment was much less for the combination (P<0.0005) than for either single treatment. Conclusions Bioluminescence imaging is an efficient way to monitor endodontic therapy. Antimicrobial PDT may have a role to play in optimized endodontic therapy. PMID:17066481

In vitro evaluation of wound healing and antimicrobial potential of ozone therapy.

PubMed

Borges, Gabriel Álvares; Elias, Silvia Taveira; da Silva, Sandra Márcia Mazutti; Magalhães, Pérola Oliveira; Macedo, Sergio Bruzadelli; Ribeiro, Ana Paula Dias; Guerra, Eliete Neves Silva

2017-03-01

Although ozone therapy is extensively applied when wound repair and antimicrobial effect are necessary, little is known about cellular mechanisms regarding this process. Thus, this study aimed to evaluate ozone cytotoxicity in fibroblasts (L929) and keratinocytes (HaCaT) cell lines, its effects on cell migration and its antimicrobial activity. Cells were treated with ozonated phosphate-buffered saline (8, 4, 2, 1, 0.5 and 0.25 μg/mL ozone), chlorhexidine 0.2% or buffered-solution, and cell viability was determined through MTT assay. The effect of ozone on cell migration was evaluated through scratch wound healing and transwell migration assays. The minimum inhibitory concentrations for Candida albicans and Staphylococcus aureus were determined. Ozone showed no cytotoxicity for the cell lines, while chlorhexidine markedly reduced cell viability. Although no significant difference between control and ozone-treated cells was observed in the scratch assay, a considerable increase in fibroblasts migration was noticed on cells treated with 8 μg/mL ozonated solution. Ozone alone did not inhibit growth of microorganisms; however, its association with chlorhexidine resulted in antimicrobial activity. This study confirms the wound healing and antimicrobial potential of ozone therapy and presents the need for studies to elucidate the molecular mechanisms through which it exerts such biological effects. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Antimicrobial photodynamic therapy of S. mutans biofilms attached to relevant dental materials.

PubMed

Zoccolillo, Michelle L; Rogers, Stephen C; Mang, Thomas S

2016-12-01

Antimicrobial Photodynamic therapy (aPDT) has demonstrated efficacy in situations where conventional antibiotic therapies can be challenged such as biofilms, gram-negative bacteria, and antimicrobial resistant organisms. Surface characteristics can affect biofilm adherence and integrity and so may modify the effectiveness of aPDT. This study investigates the killing efficacy of aPDT on S. mutans biofilms grown on relevant dental substrata, examining the killing efficacy and specifically the effects of aPDT on the biofilm matrix architecture. S. mutans (NCTC 10449) was grown in 48 hours biofilms on different substrata, specifically glass, titanium, and denture acrylic. During aPDT assays, the biofilms were treated with a purpurin based sensitizer ([25 ug/ml] in DMSO) for 30 minutes, then exposed to a 664 nm diode laser at light doses of 15, 30, and 45 J/cm 2 . Colony forming unit assays were performed to determine survival following treatment. Controls for comparison in survival assays consisted of (No light/No PS; No light/PS; and No light/DMSO). MAIR-IR spectroscopy analysis was performed to investigate aPDT effects on biofilm composition before and after jet impingement. Survival was greatly reduced in the biofilm cultures following the aPDT assays. All light doses achieved a greater then 3-log inactivation on 48 hours biofilms grown on polished denture acrylic. The higher light doses (45 and 30 J) achieved greater than 3-log inactivation in 48 hours biofilms grown on glass. The higher light doses (30 and 45 J/cm 2 ) produced a 2-log inactivation in 48 hours biofilms grown on titanium. Multiple attenuated internal reflection infrared (MAIR-IR) spectroscopy data demonstrates enhanced loss of exopolysaccharide (EPS) and Amide in the aPDT treated biofilms following jet impingement. Antimicrobial PDT experiments using a purpurin based sensitizer and laser light doses of 15, 30, and 45 J/cm 2 , against S. mutans biofilm grown on different surfaces, show the effectiveness of this therapy. In CFU survival assays, a dose response to the laser is evident. While considerable disinfection was achieved on all surfaces compared to the controls, not all surfaces could be disinfected equally. MAIR-IR spectroscopy showed that aPDT groups lost more EPS and Amide versus controls, suggesting aPDT induced biofilm embrittlement, which was revealed by jet impingement. With demonstrated efficacy against various microbes and on different substrata, antimicrobial aPDT shows potential for clinical application in biofilm-mediated diseases such as peri-implantitis and periodontitis. Lasers Surg. Med. 48:995-1005, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Treatment for bovine Escherichia coli mastitis - an evidence-based approach.

PubMed

Suojala, L; Kaartinen, L; Pyörälä, S

2013-12-01

Bovine mastitis caused by Escherichia coli can range from being a subclinical infection of the mammary gland to a severe systemic disease. Cow-dependent factors such as lactation stage and age affect the severity of coliform mastitis. Evidence for the efficacy of antimicrobial treatment for E. coli mastitis is very limited. Antimicrobial resistance is generally not a limiting factor for treatment, but it should be monitored to detect changes in resistance profiles. The only antimicrobials for which there is some scientific evidence of beneficial effects in the treatment for E. coli mastitis are fluoroquinolones and cephalosporins. Both are critically important drugs, the use of which in animals destined for food should be limited to specific indications and should be based on bacteriological diagnosis. The suggested routine protocol in dairy herds could target the primary antimicrobial treatment for mastitis, specifically infections caused by gram-positive bacteria. In E. coli mastitis with mild to moderate clinical signs, a non-antimicrobial approach (anti-inflammatory treatment, frequent milking and fluid therapy) should be the first option. In cases of severe E. coli mastitis, parenteral administration of fluoroquinolones, or third- or fourth-generation cephalosporins, is recommended due to the risk of unlimited growth of bacteria in the mammary gland and ensuing bacteremia. Evidence for the efficacy of intramammary-administered antimicrobial treatment for E. coli mastitis is so limited that it cannot be recommended. Nonsteroidal anti-inflammatory drugs have documented the efficacy in the treatment for E. coli mastitis and are recommended for supportive treatment for clinical mastitis. © 2013 John Wiley & Sons Ltd.

Effect of Photodynamic Antimicrobial Chemotherapy on Mono- and Multi-Species Cariogenic Biofilms: A Literature Review

PubMed Central

de Freitas, Maria Tayara Marques; Soares, Talyta Teixeira; Aragão, Maria Gerusa Brito; Lima, Ramille Araújo; Duarte, Simone

2017-01-01

Abstract Objective: The aim of this literature review is to study the effect of photodynamic antimicrobial chemotherapy (PACT) on mono- and multi-species cariogenic biofilms. Methods: To this purpose, the database, PubMed, was searched using the descriptors, photodynamic therapy, antimicrobial photodynamic chemotherapy, and photoinactivation, associated with the mandatory presence of the word biofilm. A total of 98 references published from 2003 to 2016 were selected. Moreover, literature reviews (15), investigations that did not have biofilms related to dental caries (65), and those that did not have Streptococcus mutans count as an outcome (7) were excluded, yielding a final amount of 11 publications. Results: The results revealed that Toluidine Blue O was the most used photosensitizer. Among the sources of light, light-emitting diode was the choice, and the biofilm models varied between in vitro and in situ. Multi-species biofilms were more resistant to the antimicrobial effects of PACT due to the thickness and complexity they have, which impede the penetration of the photosensitizer. This fact may also be associated with the type of photosensitizer used as well as with the light exposure time since the antimicrobial effect seems to be dose dependent. Despite this, in all the included publications, the therapy was effective in reducing S. mutans count. Conclusions: This review demonstrated that under different conditions, PACT is effective in reducing S. mutans count in monospecies biofilms. Multi-species biofilms were more resistant to the antimicrobial action of the therapy, possibly due to their thickness and complexity. PMID:28121497

Impact of an Antimicrobial Stewardship Care Bundle to Improve the Management of Patients with Suspected or Confirmed Urinary Tract Infection.

PubMed

Collins, Curtis D; Kabara, Jared J; Michienzi, Sarah M; Malani, Anurag N

2016-12-01

Implementation of an antimicrobial stewardship program bundle for urinary tract infections among 92 patients led to a higher rate of discontinuation of therapy for asymptomatic bacteriuria (52.4% vs 12.5%; P =.004), more appropriate durations of therapy (88.7% vs 63.6%; P =.001), and significantly higher overall bundle compliance (75% vs 38.2%; P < .001). Infect Control Hosp Epidemiol 2016;1499-1501.

Effect of different scenarios for selective dry-cow therapy on udder health, antimicrobial usage, and economics.

PubMed

Scherpenzeel, C G M; den Uijl, I E M; van Schaik, G; Riekerink, R G M Olde; Hogeveen, H; Lam, T J G M

2016-05-01

The goal of dry-cow therapy (DCT) is to reduce the prevalence of intramammary infections (IMI) by eliminating existing IMI at drying off and preventing new IMI from occurring during the dry period. Due to public health concerns, however, preventive use of antimicrobials has become questionable. In this study, we evaluated the effects of 8 scenarios for selecting animals for DCT, taking into account variation in parity and cow-level somatic cell count (SCC) at drying off. The aim of this study was to evaluate udder health, antimicrobial usage, and economics at the herd level when using different scenarios for selecting cows for DCT. To enable calculation and comparison of the effects of different scenarios to select cows for DCT in an "average" herd, we created an example herd, with a virtual herd size of 100 dairy cows to be calving during a year. Udder health, antimicrobial usage, and economics were evaluated during the dry period and the first 100 d in lactation, the period during which the greatest effect of DCT is expected. This leads to an estimated 13,551 cow-days at risk during a year in a 100-cow dairy herd. In addition to a blanket DCT (BDCT) scenario, we developed 7 scenarios to select cows for DCT based on SCC. The scenarios covered a range of possible approaches to select low-SCC cows for DCT, all based on cow-level SCC thresholds on the last milk recording before drying off. The incidence rate of clinical mastitis in the example herd varied from 11.6 to 14.5 cases of clinical mastitis per 10,000 cow-days at risk in the different scenarios, and the prevalence of subclinical mastitis varied from 38.8% in scenario 1 (BDCT) to 48.3% in scenario 8. Total antimicrobial usage for DCT and clinical mastitis treatment varied over the scenarios from 1.27 (scenario 8) to 3.15 animal daily dosages (BDCT), leading to a maximum reduction in antimicrobial usage of 60% for scenario 8 compared with BDCT. The total costs for each of the scenarios showed little variation, varying from €4,893 for scenario 5 to €5,383 for scenario 8. The effect of selective DCT compared with BDCT on udder health, antimicrobial usage, and economics is influenced by the SCC criteria used to select cows for DCT. Scenario 2 resulted in the lowest increases in clinical and subclinical mastitis compared with BDCT. The greatest reduction in antimicrobial usage was achieved under scenario 8. From an economic perspective, lowest costs were achieved with scenario 5. Drying off dairy cows with antimicrobials has an effect on udder health, antimicrobial usage, and economics. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Antimicrobial Stewardship and Urinary Tract Infections

PubMed Central

Abbo, Lilian M.; Hooton, Thomas M.

2014-01-01

Urinary tract infections are the most common bacterial infections encountered in ambulatory and long-term care settings in the United States. Urine samples are the largest single category of specimens received by most microbiology laboratories and many such cultures are collected from patients who have no or questionable urinary symptoms. Unfortunately, antimicrobials are often prescribed inappropriately in such patients. Antimicrobial use, whether appropriate or inappropriate, is associated with the selection for antimicrobial-resistant organisms colonizing or infecting the urinary tract. Infections caused by antimicrobial-resistant organisms are associated with higher rates of treatment failures, prolonged hospitalizations, increased costs and mortality. Antimicrobial stewardship consists of avoidance of antimicrobials when appropriate and, when antimicrobials are indicated, use of strategies to optimize the selection, dosing, route of administration, duration and timing of antimicrobial therapy to maximize clinical cure while limiting the unintended consequences of antimicrobial use, including toxicity and selection of resistant microorganisms. This article reviews successful antimicrobial stewardship strategies in the diagnosis and treatment of urinary tract infections. PMID:27025743

Failure mode and effects analysis to reduce risk of anticoagulation levels above the target range during concurrent antimicrobial therapy.

PubMed

Daniels, Lisa M; Barreto, Jason N; Kuth, John C; Anderson, Jeremy R; Zhang, Beilei; Majka, Andrew J; Morgenthaler, Timothy I; Tosh, Pritish K

2015-07-15

A failure mode and effects analysis (FMEA) was conducted to analyze the clinical and operational processes leading to above-target International Normalized Ratios (INRs) in warfarin-treated patients receiving concurrent antimicrobial therapy. The INRs of patients on long-term warfarin therapy who received a course of trimethoprim-sulfamethoxazole, metronidazole, fluconazole, miconazole, or voriconazole (highly potentiating antimicrobials, or HPAs) between September 1 and December 31, 2011, were compared with patients on long-term warfarin therapy who did not receive any antimicrobial during the same period. A multidisciplinary team of physicians, pharmacists, and a systems analyst was then formed to complete a step-by-step outline of the processes involved in warfarin management and concomitant HPA therapy, followed by an FMEA. Patients taking trimethoprim-sulfamethoxazole, metronidazole, or fluconazole demonstrated a significantly increased risk of having an INR of >4.5. The FMEA identified 134 failure modes. The most common failure modes were as follows: (1) electronic medical records did not identify all patients receiving warfarin, (2) HPA prescribers were unaware of recommended warfarin therapy when HPAs were prescribed, (3) HPA prescribers were unaware that a patient was taking warfarin and that the drug interaction is significant, and (4) warfarin managers were unaware that an HPA had been prescribed for a patient. An FMEA determined that the risk of adverse events caused by concomitantly administering warfarin and HPAs can be decreased by preemptively identifying patients receiving warfarin, having a care process in place, alerting providers about the patient's risk status, and notifying providers at the anticoagulation clinic. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Usability application of multiplex polymerase chain reaction in the diagnosis of microorganisms isolated from urine of patients treated in cancer hospital

PubMed Central

Cybulski, Zefiryn; Schmidt, Katarzyna; Grabiec, Alicja; Talaga, Zofia; Bociąg, Piotr; Wojciechowicz, Jacek; Roszak, Andrzej; Kycler, Witold

2013-01-01

Background The objective of this study was: i) to compare the results of urine culture with polymerase chain reaction (PCR) -based detection of microorganisms using two commercially available kits, ii) to assess antimicrobial susceptibility of urine isolates from cancer patients to chosen antimicrobial drugs and, if necessary, to update the recommendation of empirical therapy. Materials and methods. A one-year hospital-based prospective study has been conducted in Greater Poland Cancer Centre and Genetic Medicine Laboratory CBDNA Research Centre in 2011. Urine cultures and urine PCR assay from 72 patients were examined Results Urine cultures and urine PCR assay from 72 patients were examined. Urine samples were positive for 128 strains from which 95 (74%) were identical in both tests. The most frequently isolated bacteria in both culture and PCR assay were coliform organisms and Enterococcus spp. The Gram negative bacilli were most resistant to cotrimoxazol. 77.2% of these bacilli and 100% of E. faecalis and S. agalactiae were sensitive to amoxicillin-clavulanic acid. 4.7% of Gram positive cocci were resistant to nitrofurantoin. Conclusions The PCR method quickly finds the causative agent of urinary tract infection (UTI) and, therefore, it can help with making the choice of the proper antimicrobial therapy at an early stage. It appears to be a viable alternative to the recommendations made in general treatment guidelines, in cases where diversified sensitivity patterns of microorganisms have been found. PMID:24133395

Antimicrobial drug use in Austrian pig farms: plausibility check of electronic on-farm records and estimation of consumption.

PubMed

Trauffler, M; Griesbacher, A; Fuchs, K; Köfer, J

2014-10-25

Electronic drug application records from farmers from 75 conventional pig farms were revised and checked for their plausibility. The registered drug amounts were verified by comparing the farmers' records with veterinarians' dispensary records. The antimicrobial consumption was evaluated from 2008 to 2011 and expressed in weight of active substance(s), number of used daily doses (nUDD), number of animal daily doses (nADD) and number of product-related daily doses (nPrDD). All results were referred to one year and animal bodyweight (kg biomass). The data plausibility proof revealed about 14 per cent of unrealistic drug amount entries in the farmers' records. The annual antimicrobial consumption was 33.9 mg/kg/year, 4.9 UDDkg/kg/year, 1.9 ADDkg/kg/year and 2.5 PrDDkg/kg/year (average). Most of the antimicrobials were applied orally (86 per cent) and at group-level. Main therapy indications were metaphylactic/prophylactic measures (farrow-to-finish and fattening farms) or digestive tract diseases (breeding farms). The proportion of the 'highest priority critically important antimicrobials' was low (12 per cent). After determination of a threshold value, farms with a high antimicrobial use could be detected. Statistical tests showed that the veterinarian had an influence on the dosage, the therapy indication and the active substance. Orally administered antimicrobials were mostly underdosed, parenterally administered antimicrobials rather correctly or overdosed. British Veterinary Association.

Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial.

PubMed

Kaasch, Achim J; Fätkenheuer, Gerd; Prinz-Langenohl, Reinhild; Paulus, Ursula; Hellmich, Martin; Weiß, Verena; Jung, Norma; Rieg, Siegbert; Kern, Winfried V; Seifert, Harald

2015-10-09

Current guidelines recommend that patients with Staphylococcus aureus bloodstream infection (SAB) are treated with long courses of intravenous antimicrobial therapy. This serves to avoid SAB-related complications such as relapses, local extension and distant metastatic foci. However, in certain clinical scenarios, the incidence of SAB-related complications is low. Patients with a low-risk for complications may thus benefit from an early switch to oral medication through earlier discharge and fewer complications of intravenous therapy. The major objective for the SABATO trial is to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST). The trial is designed as randomized, parallel-group, observer-blinded, clinical non-inferiority trial. The primary endpoint is the occurrence of a SAB-related complication (relapsing SAB, deep-seated infection, and attributable mortality) within 90 days. Secondary endpoints are the length of hospital stay; 14-day, 30-day, and 90-day mortality; and complications of intravenous therapy. Patients with SAB who have received 5 to 7 full days of adequate intravenous antimicrobial therapy are eligible. Main exclusion criteria are polymicrobial bloodstream infection, signs and symptoms of complicated SAB (deep-seated infection, hematogenous dissemination, septic shock, and prolonged bacteremia), the presence of a non-removable foreign body, and severe comorbidity. Patients will receive either OST or IST with a protocol-approved antimicrobial and are followed up for 90 days. Four hundred thirty patients will be randomized 1:1 in two study arms. Efficacy regarding incidence of SAB-related complications is tested sequentially with a non-inferiority margin of 10 and 5 percentage points. The SABATO trial assesses whether early oral switch therapy is safe and effective for patients with low-risk SAB. Regardless of the result, this pragmatic trial will strongly influence the standard of care in SAB. ClinicalTrials.gov NCT01792804 registered 13 February 2013; German Clinical trials register DRKS00004741 registered 4 October 2013, EudraCT 2013-000577-77 . First patient randomized on 20 December 2013.

Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

PubMed

Santolaya, M E; Alvarez, A M; Acuña, M; Avilés, C L; Salgado, C; Tordecilla, J; Varas, M; Venegas, M; Villarroel, M; Zubieta, M; Toso, A; Bataszew, A; Farfán, M J; de la Maza, V; Vergara, A; Valenzuela, R; Torres, J P

2017-03-01

To determine efficacy and safety of withholding antimicrobials in children with cancer, fever and neutropenia (FN) with a demonstrated respiratory viral infection. Prospective, multicentre, randomized study in children presenting with FN at five hospitals in Santiago, Chile, evaluated at admission for diagnosis of bacterial and viral pathogens including PCR-microarray for 17 respiratory viruses. Children positive for a respiratory virus, negative for a bacterial pathogen and with a favourable evolution after 48 h of antimicrobial therapy were randomized to either maintain or withhold antimicrobials. Primary endpoint was percentage of episodes with uneventful resolution. Secondary endpoints were days of fever/hospitalization, bacterial infection, sepsis, admission to paediatric intensive care unit (PICU) and death. A total of 319 of 951 children with FN episodes recruited between July 2012 and December 2015 had a respiratory virus as a unique identified microorganism, of which 176 were randomized, 92 to maintain antimicrobials and 84 to withdraw. Median duration of antimicrobial use was 7 days (range 7-9 days) versus 3 days (range 3-4 days), with similar frequency of uneventful resolution (89/92 (97%) and 80/84 (95%), respectively, not significant; OR 1.48; 95% CI 0.32-6.83, p 0.61), and similar number of days of fever (2 versus 1), days of hospitalization (6 versus 6) and bacterial infections throughout the episode (2%-1%), with one case of sepsis requiring admission to PICU in the group that maintained antimicrobials, without any deaths. The reduction of antimicrobials in children with FN and respiratory viral infections, based on clinical and microbiological/molecular diagnostic criteria, should favour the adoption of evidence-based management strategies in this population. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.

PubMed

Weiss, Scott L; Fitzgerald, Julie C; Balamuth, Fran; Alpern, Elizabeth R; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M; Thomas, Neal J

2014-11-01

Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Retrospective observational study. PICU at an academic medical center. One hundred thirty patients treated for severe sepsis or septic shock. None. We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure-free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74-277 min) and to first appropriate antimicrobial was 177 minutes (90-550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2) and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure-free days (16 [interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04). Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.

Delayed Antimicrobial Therapy Increases Mortality and Organ Dysfunction Duration in Pediatric Sepsis

PubMed Central

Weiss, Scott L.; Fitzgerald, Julie C.; Balamuth, Fran; Alpern, Elizabeth R.; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M.; Thomas, Neal J.

2014-01-01

Objectives Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Design Retrospective observational study. Setting PICU at an academic medical center. Patients One hundred thirty patients treated for severe sepsis or septic shock. Interventions None. Measurements and Main Results We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure–free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74–277 min) and to first appropriate antimicrobial was 177 minutes (90–550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27–12.06) and 3.59 (95% CI, 1.09–11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45–16.2) and 4.92 (95% CI, 1.30–18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure–free days (16 [interquartile range, 1–23] vs 20 [interquartile range, 6–26]; p = 0.04). Conclusions Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis. PMID:25148597

Impact of Matrix-Assisted Laser Desorption and Ionization Time-of-Flight and Antimicrobial Stewardship Intervention on Treatment of Bloodstream Infections in Hospitalized Children.

PubMed

Malcolmson, Caroline; Ng, Karen; Hughes, Shevaun; Kissoon, Niranjan; Schina, Jillian; Tilley, Peter A; Roberts, Ashley

2017-06-01

Early definitive identification of infectious pathogens coupled with antimicrobial stewardship interventions allow for targeted and timely administration of antimicrobials. We investigated the combined impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology and an antimicrobial stewardship program (ASP) in pediatric patients with blood stream infections (BSIs). This is a single-center study comparing a control group of patients from October 2009 to July 2010 with BSIs to a cohort of patients postimplementation of MALDI-TOF and an ASP, from October 2013 to July 2014. Primary outcome was time to optimal therapy. Secondary outcomes included time to effective therapy, 30-day all-cause mortality, 30-day readmission rate, hospital length of stay, and intensive care admission. One hundred episodes of BSIs were identified in the preintervention period, and 121 episodes were identified in the postintervention period. Time from blood culture collection to organism identification was significantly reduced in the prospective cohort compared with historical controls (18.8 vs 43.7 hours, respectively). A total of 73 ASP interventions were made on the treatment of BSIs in the postintervention period. Combined use of MALDI-TOF and ASP significantly reduced time to optimal therapy (77.0 to 54.2 hours, P < .001). In the subgroup analysis of Gram-negative bacteremia, time to effective and optimal therapy were significantly reduced (2.0 vs 0.7 hours and 146.8 vs 48.0 hours, respectively). There were no significant differences in clinical outcomes. The combined use of MALDI-TOF and ASP allows early optimization of antimicrobial therapy in pediatric inpatients with BSIs. © The Author 2016. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Saccharomyces cerevisiae colonization associated with fecal microbiota treatment failure

USDA-ARS?s Scientific Manuscript database

Background: Fecal microbiota therapy (FMT) has emerged as the gold standard for treatment of persistent, symptomatic Clostridium difficile infection (CDI) that does not respond to conventional antimicrobial treatment. Probiotics are commonly recommended in addition to antimicrobial treatment for CD...

A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens

PubMed Central

Wittebole, Xavier; De Roock, Sophie; Opal, Steven M

2014-01-01

The seemingly inexorable spread of antibiotic resistance genes among microbial pathogens now threatens the long-term viability of our current antimicrobial therapy to treat severe bacterial infections such as sepsis. Antibiotic resistance is reaching a crisis situation in some bacterial pathogens where few therapeutic alternatives remain and pan-resistant strains are becoming more prevalent. Non-antibiotic therapies to treat bacterial infections are now under serious consideration and one possible option is the therapeutic use of specific phage particles that target bacterial pathogens. Bacteriophage therapy has essentially been re-discovered by modern medicine after widespread use of phage therapy in the pre-antibiotic era lost favor, at least in Western countries, after the introduction of antibiotics. We review the current therapeutic rationale and clinical experience with phage therapy as a treatment for invasive bacterial infection as novel alternative to antimicrobial chemotherapy. PMID:23973944

Molecular Detection of Helicobacter pylori and its Antimicrobial Resistance in Brazzaville, Congo.

PubMed

Ontsira Ngoyi, Esther Nina; Atipo Ibara, Blaise Irénée; Moyen, Rachelle; Ahoui Apendi, Philestine Clausina; Ibara, Jean Rosaire; Obengui, O; Ossibi Ibara, Roland Bienvenu; Nguimbi, Etienne; Niama, Rock Fabien; Ouamba, Jean Maurille; Yala, Fidèle; Abena, Ange Antoine; Vadivelu, Jamuna; Goh, Khean Lee; Menard, Armelle; Benejat, Lucie; Sifre, Elodie; Lehours, Philippe; Megraud, Francis

2015-08-01

Helicobacter pylori infection is involved in several gastroduodenal diseases which can be cured by antimicrobial treatment. The aim of this study was to determine the prevalence of H. pylori infection and its bacterial resistance to clarithromycin, fluoroquinolones, and tetracycline in Brazzaville, Congo, by using molecular methods. A cross- sectional study was carried out between September 2013 and April 2014. Biopsy specimens were obtained from patients scheduled for an upper gastrointestinal endoscopy and were sent to the French National Reference Center for Campylobacters and Helicobacters where they were tested by molecular methods for detection of H. pylori and clarithromycin resistance by real-time PCR using a fluorescence resonance energy transfer-melting curve analysis (FRET-MCA) protocol, for detection of tetracycline resistance by real-time PCR on 16S rRNA genes (rrnA and rrnB), for detection of point mutations in the quinolone resistance-determining regions (QRDR) of H. pylori gyrA gene, associated with resistance to quinolones, by PCR and sequencing. This study showed a high H. pylori prevalence (89%), low rates of clarithromycin and tetracycline resistance (1.7% and 2.5%, respectively), and a high rate of quinolone resistance (50%). Therefore, the use of standard clarithromycin-based triple therapy is still possible as an empiric first-line treatment as well as prescription of bismuth-based quadruple therapy, which includes tetracycline, but not a levofloxacin-based triple therapy because of the high rate of resistance to fluoroquinolones. © 2015 John Wiley & Sons Ltd.

Antimicrobial Therapy for Legionnaire's Disease: Antibiotic Stewardship Implications.

PubMed

Cunha, Cheston B; Cunha, Burke A

2017-03-01

Legionnaire's disease is a common cause of community-acquired pneumonia (CAP). Although no single clinical feature is diagnostic, if characteristic extrapulmonary findings are present a presumptive clinical syndromic diagnosis is possible. Depending on geographic location, season, and physician awareness, Legionnaire's disease may be included in the differential diagnosis of CAP. Some antibiotics effective against Legionella sp are also effective in treating the typical bacterial causes of CAP. From an antimicrobial stewardship program (ASP) perspective, monotherapy is preferred to double-drug therapy. From an ASP and pharmacoeconomic standpoint, monotherapy with doxycycline or a respiratory quinolone provides optimal cost effective therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Rickettsial infection of the central nervous system: the role of prompt antimicrobial therapy.

PubMed

Shaked, Y

1991-04-01

Rickettsial diseases of man, which are prevalent in all the continents (except Antartica) continue to be a major health problem in tropical and temperate parts of the world. Rickettsioses must be considered in every traveller seeking medical attention soon after returning from endemic areas, since the disease can be associated with significant morbidity. When a definite diagnosis has been made by specific serological tests, prompt antimicrobial therapy is indicated. A tetracycline should be regarded as the drug of choice due to its high efficacy, low toxicity, superior in vitro activity and the possibility of relapse which can follow chloramphenicol therapy.

Antimicrobial Photodynamic Inactivation and Antitumor Photodynamic Therapy with Fullerenes

NASA Astrophysics Data System (ADS)

de Freitas, Lucas F.

2016-04-01

This book provides detailed and current information on using fullerenes (bucky-balls) in photodynamic therapy (PDT), one of the most actively studied applications of photonic science in healthcare. This will serve as a useful source for researchers working in photomedicine and nanomedicine, especially those who are investigating PDT for cancer treatment and infectious disease treatment. The book runs the gamut from an introduction to the history and chemistry of fullerenes and some basic photochemistry, to the application of fullerenes as photosensitizers for cancer and antimicrobial inactivation.

Comparative minimum inhibitory and mutant prevention drug concentrations of enrofloxacin, ceftiofur, florfenicol, tilmicosin and tulathromycin against bovine clinical isolates of Mannheimia haemolytica.

PubMed

Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J J; Hesje, C E

2012-11-09

Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin. Copyright © 2012 Elsevier B.V. All rights reserved.

Antimicrobial stewardship – can we afford to do without it?

PubMed Central

Aryee, Anna; Price, Nicholas

2015-01-01

Antimicrobial resistance (AMR) is a rapidly developing and alarming global threat which has been highlighted by national governments and public health bodies including the World Health Organization. The spectre of a ‘post-antibiotic era’ is a real possibility unless curtailing the development and spread of these organisms is given high priority. Numerous studies have shown that AMR is associated with worse outcomes for patients and higher healthcare costs. While clinical data from low and middle income countries is lacking, there is increasing evidence that the problem in these areas is as great, or even greater, than in high income nations. Of the many drivers behind the development of AMR, the most significant is selection pressure caused by antibiotic use. Antimicrobial stewardship programmes are a set of interventions that aim to ensure the judicious use of antimicrobials by preventing their unnecessary use, and by providing targeted and limited therapy in situations where they are warranted. The ultimate goal of these programmes is to provide effective antimicrobial therapy whilst safeguarding their effectiveness for future generations. Whilst they do require an initial investment, they have been shown to be an effective way of controlling antimicrobial use, and have been associated with improved patient outcomes and reduced healthcare costs. PMID:24803175

Non-culture Neisseria gonorrhoeae molecular penicillinase production surveillance demonstrates the long-term success of empirical dual therapy and informs gonorrhoea management guidelines in a highly endemic setting.

PubMed

Speers, David J; Fisk, Rachel E; Goire, Namraj; Mak, Donna B

2014-05-01

Unlike most of the world, penicillin resistance in Neisseria gonorrhoeae from remote regions of Western Australia (WA) with high gonorrhoea notification rates has not increased despite many years of empirical oral therapy. With the advent of non-culture molecular diagnosis of gonorrhoea and the consequent decline in culture-based susceptibility, it is imperative to ensure the ongoing reliability of combination oral azithromycin, amoxicillin and probenecid for uncomplicated gonorrhoea in this setting. PCR-based non-culture N. gonorrhoeae antimicrobial resistance surveillance for penicillinase production was therefore employed. Genital and non-genital specimens that were PCR-positive for N. gonorrhoeae were assessed for penicillinase production by detection of the N. gonorrhoeae TEM-1 plasmid using specific real-time PCR. In remote regions of WA where gonorrhoea is highly endemic, <5% of N. gonorrhoeae isolates were penicillinase-producing. This contrasts with rates of up to 20% observed in the more densely populated metropolitan and rural regions. In the era of molecular diagnosis of gonorrhoea, non-culture-based antimicrobial resistance surveillance proved useful when developing evidence-based guidelines for the clinical management of locally acquired gonorrhoea in highly endemic regions in WA. The continued efficacy of combination oral amoxicillin, probenecid and azithromycin therapy despite many years of use in a setting highly endemic for gonorrhoea may explain the low rate of penicillin resistance in these remote regions and supports the concept of adding azithromycin to β-lactam antibiotics to help delay the emergence of multiresistant N. gonorrhoeae.

Antibiotic management of complicated intra-abdominal infections in adults: The Asian perspective

PubMed Central

Kurup, Asok; Liau, Kui-Hin; Ren, Jianan; Lu, Min-Chi; Navarro, Narciso S.; Farooka, Muhammad Waris; Usman, Nurhayat; Destura, Raul V.; Sirichindakul, Boonchoo; Tantawichien, Terapong; Lee, Christopher K.C.; Solomkin, Joseph S.

2014-01-01

Regional epidemiological data and resistance profiles are essential for selecting appropriate antibiotic therapy for intra-abdominal infections (IAIs). However, such information may not be readily available in many areas of Asia and current international guidelines on antibiotic therapy for IAIs are for Western countries, with the most recent guidance for the Asian region dating from 2007. Therefore, the Asian Consensus Taskforce on Complicated Intra-Abdominal Infections (ACT-cIAI) was convened to develop updated recommendations for antibiotic management of complicated IAIs (cIAIs) in Asia. This review article is based on a thorough literature review of Asian and international publications related to clinical management, epidemiology, microbiology, and bacterial resistance patterns in cIAIs, combined with the expert consensus of the Taskforce members. The microbiological profiles of IAIs in the Asian region are outlined and compared with Western data, and the latest available data on antimicrobial resistance in key pathogens causing IAIs in Asia is presented. From this information, antimicrobial therapies suitable for treating cIAIs in patients in Asian settings are proposed in the hope that guidance relevant to Asian practices will prove beneficial to local physicians managing IAIs. PMID:25568794

MYCIN II: design and implementation of a therapy reference with complex content-based indexing.

PubMed Central

Kim, D. K.; Fagan, L. M.; Jones, K. T.; Berrios, D. C.; Yu, V. L.

1998-01-01

We describe the construction of MYCIN II, a prototype system that provides for content-based markup and search of a forthcoming clinical therapeutics textbook, Antimicrobial Therapy and Vaccines. Existing commercial search technology for digital references utilizes generic tools such as textword-based searches with geographical or statistical refinements. We suggest that the drawbacks of such systems significantly restrict their use in everyday clinical practice. This is in spite of the fact that there is a great need for the information contained within these same references. The system we describe is intended to supplement keyword searching so that certain important questions can be asked easily and can be answered reliably (in terms of precision and recall). Our method attacks this problem in a restricted domain of knowledge-clinical infectious disease. For example, we would like to be able to answer the class of questions exemplified by the following query: "What antimicrobial agents can be used to treat endocarditis caused by Eikenella corrodens?" We have compiled and analyzed a list of such questions to develop a concept-based markup scheme. This scheme was then applied within an HTML markup to electronically "highlight" passages from three textbook chapters. We constructed a functioning web-based search interface. Our system also provides semi-automated querying of PubMed using our concept markup and the user's actions as a guide. PMID:9929205

MYCIN II: design and implementation of a therapy reference with complex content-based indexing.

PubMed

Kim, D K; Fagan, L M; Jones, K T; Berrios, D C; Yu, V L

1998-01-01

We describe the construction of MYCIN II, a prototype system that provides for content-based markup and search of a forthcoming clinical therapeutics textbook, Antimicrobial Therapy and Vaccines. Existing commercial search technology for digital references utilizes generic tools such as textword-based searches with geographical or statistical refinements. We suggest that the drawbacks of such systems significantly restrict their use in everyday clinical practice. This is in spite of the fact that there is a great need for the information contained within these same references. The system we describe is intended to supplement keyword searching so that certain important questions can be asked easily and can be answered reliably (in terms of precision and recall). Our method attacks this problem in a restricted domain of knowledge-clinical infectious disease. For example, we would like to be able to answer the class of questions exemplified by the following query: "What antimicrobial agents can be used to treat endocarditis caused by Eikenella corrodens?" We have compiled and analyzed a list of such questions to develop a concept-based markup scheme. This scheme was then applied within an HTML markup to electronically "highlight" passages from three textbook chapters. We constructed a functioning web-based search interface. Our system also provides semi-automated querying of PubMed using our concept markup and the user's actions as a guide.

Clinical effect of a multidisciplinary team approach to the initial treatment of patients with hospital-acquired bloodstream infections at a Japanese university hospital.

PubMed

Tsukamoto, Hitoshi; Higashi, Takashi; Nakamura, Toshiaki; Yano, Ryoichi; Hida, Yukio; Muroi, Yoko; Ikegaya, Satoshi; Iwasaki, Hiromichi; Masada, Mikio

2014-09-01

Hospital-acquired bloodstream infections (BSIs) are significant causes of mortality, and strategies to improve outcomes are needed. We aimed to evaluate the clinical efficacy of a multidisciplinary infection control team (ICT) approach to the initial treatment of patients with hospital-acquired BSI. A before-after quasiexperimental study of patients with hospital-acquired BSI was performed in a Japanese university hospital. The ICT provided immediate recommendations to the attending physician about appropriate antimicrobial therapy and management after reviewing blood cultures, Gram's stain, final organism, and antimicrobial susceptibility results. The sample included 469 patients with hospital-acquired BSI (n = 210, preintervention group; n = 259, postintervention group). There were no significant differences between the groups in background or microbiologic characteristics. The 30-day mortality was significantly lower and significantly more patients received appropriate antimicrobial therapy in the postintervention group (22.9% vs 14.3%; P = .02 and 86.5% vs 69.0%; P < .001, respectively). Multivariate analysis confirmed that the ICT intervention was significantly associated with appropriate antimicrobial therapy (odds ratio, 2.22; 95% confidence interval, 1.27-3.89) and 30-day mortality (odds ratio, 0.49; 95% confidence interval, 0.25-0.95). A timely multidisciplinary team approach decreases the delay of appropriate antimicrobial treatment and may improve HABSI patient outcomes. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Risk Factors for Severe Infection, Hospitalization, and Prolonged Antimicrobial Therapy in Patients with Babesiosis.

PubMed

Mareedu, Neeharik; Schotthoefer, Anna M; Tompkins, Jason; Hall, Matthew C; Fritsche, Thomas R; Frost, Holly M

2017-10-01

Babesiosis is an emerging tick-borne disease transmitted by the hard tick Ixodes scapularis , which also transmits Lyme disease. Better gradation of prognostic indicators are needed to determine which patients may develop serious complications requiring hospitalization, and to provide early guidance on appropriate therapy. In this study, we evaluated 128 patients with smear or real time polymerase chain reaction-confirmed Babesia microti infections over a period of 16 years. Patients with asplenia or immunocompromising conditions were more likely to have severe infection ( P < 0.01), require hospitalization ( P < 0.01), or receive prolonged courses of antimicrobials ( P < 0.01). Nausea or vomiting ( P < 0.01) and diarrhea ( P < 0.01) along with hyperbilirubinemia ( P < 0.01) were predictive of severe infection, hospitalization, and prolonged antimicrobial therapy. Patients with concurrent Lyme disease were less likely to require hospitalization and had similar severity of disease and length of antibiotic treatment compared with those without Lyme disease.

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

PubMed Central

Dadachova, Ekaterina; Nakouzi, Antonio; Bryan, Ruth A.; Casadevall, Arturo

2003-01-01

There is an urgent need for new antimicrobial therapies to combat drug resistance, new pathogens, and the relative inefficacy of current therapy in compromised hosts. Ionizing radiation can kill microorganisms quickly and efficiently, but this modality has not been exploited as a therapeutic antimicrobial strategy. We have developed methods to target ionizing radiation to a fungal cell by labeling a specific mAb with the therapeutic radioisotopes Rhenium-188 and Bismuth-213. Radiolabeled antibody killed cells of human pathogenic fungus Cryptococcus neoformans in vitro, thus converting an antibody with no inherent antifungal activity into a microbicidal molecule. Administration of radiolabeled antibody to mice with C. neoformans infection delivered 213Bi and 188Re to the sites of infection, reduced their organ fungal burden, and significantly prolonged their survival without apparent toxicity. This study establishes the principle that targeted radiation can be used for the therapy of an infectious disease, and suggests that it may have wide applicability as an antimicrobial strategy. PMID:12930899

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

NASA Astrophysics Data System (ADS)

Dadachova, Ekaterina; Nakouzi, Antonio; Bryan, Ruth A.; Casadevall, Arturo

2003-09-01

There is an urgent need for new antimicrobial therapies to combat drug resistance, new pathogens, and the relative inefficacy of current therapy in compromised hosts. Ionizing radiation can kill microorganisms quickly and efficiently, but this modality has not been exploited as a therapeutic antimicrobial strategy. We have developed methods to target ionizing radiation to a fungal cell by labeling a specific mAb with the therapeutic radioisotopes Rhenium-188 and Bismuth-213. Radiolabeled antibody killed cells of human pathogenic fungus Cryptococcus neoformans in vitro, thus converting an antibody with no inherent antifungal activity into a microbicidal molecule. Administration of radiolabeled antibody to mice with C. neoformans infection delivered 213Bi and 188Re to the sites of infection, reduced their organ fungal burden, and significantly prolonged their survival without apparent toxicity. This study establishes the principle that targeted radiation can be used for the therapy of an infectious disease, and suggests that it may have wide applicability as an antimicrobial strategy.

Selective killing of Helicobacter pylori with pH-responsive helix–coil conformation transitionable antimicrobial polypeptides

PubMed Central

Xiong, Menghua; Bao, Yan; Xu, Xin; Wang, Hua; Han, Zhiyuan; Wang, Zhiyu; Liu, Yeqing; Huang, Songyin; Song, Ziyuan; Chen, Jinjing; Peek, Richard M.; Yin, Lichen; Chen, Lin-Feng; Cheng, Jianjun

2017-01-01

Current clinical treatment of Helicobacter pylori infection, the main etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma, requires a combination of at least two antibiotics and one proton pump inhibitor. However, such triple therapy suffers from progressively decreased therapeutic efficacy due to the drug resistance and undesired killing of the commensal bacteria due to poor selectivity. Here, we report the development of antimicrobial polypeptide-based monotherapy, which can specifically kill H. pylori under acidic pH in the stomach while inducing minimal toxicity to commensal bacteria under physiological pH. Specifically, we designed a class of pH-sensitive, helix–coil conformation transitionable antimicrobial polypeptides (HCT-AMPs) (PGA)m-r-(PHLG-MHH)n, bearing randomly distributed negatively charged glutamic acid and positively charged poly(γ-6-N-(methyldihexylammonium)hexyl-l-glutamate) (PHLG-MHH) residues. The HCT-AMPs showed unappreciable toxicity at physiological pH when they adopted random coiled conformation. Under acidic condition in the stomach, they transformed to the helical structure and exhibited potent antibacterial activity against H. pylori, including clinically isolated drug-resistant strains. After oral gavage, the HCT-AMPs afforded comparable H. pylori killing efficacy to the triple-therapy approach while inducing minimal toxicity against normal tissues and commensal bacteria, in comparison with the remarkable killing of commensal bacteria by 65% and 86% in the ileal contents and feces, respectively, following triple therapy. This strategy renders an effective approach to specifically target and kill H. pylori in the stomach while not harming the commensal bacteria/normal tissues. PMID:29133389

Antimicrobial Resistance and Reduced Susceptibility in Clostridium difficile: Potential Consequences for Induction, Treatment, and Recurrence of C. difficile Infection

PubMed Central

Baines, Simon D.; Wilcox, Mark H.

2015-01-01

Clostridium difficile infection (CDI) remains a substantial burden on healthcare systems and is likely to remain so given our reliance on antimicrobial therapies to treat bacterial infections, especially in an aging population in whom multiple co-morbidities are common. Antimicrobial agents are a key component in the aetiology of CDI, both in the establishment of the infection and also in its treatment. The purpose of this review is to summarise the role of antimicrobial agents in primary and recurrent CDI; assessing why certain antimicrobial classes may predispose to the induction of CDI according to a balance between antimicrobial activity against the gut microflora and C. difficile. Considering these aspects of CDI is important in both the prevention of the infection and in the development of new antimicrobial treatments. PMID:27025625

Role of Combination Antimicrobial Therapy for Vancomycin-Resistant Enterococcus faecium Infections: Review of the Current Evidence.

PubMed

Yim, Juwon; Smith, Jordan R; Rybak, Michael J

2017-05-01

Enterococcus species are the second most common cause of nosocomial infections in the United States and are particularly concerning in critically ill patients with preexisting comorbid conditions. Rising resistance to antimicrobials that were historically used as front-line agents for treatment of enterococcal infections, such as ampicillin, vancomycin, and aminoglycosides, further complicates the treatment of these infections. Of particular concern are Enterococcus faecium strains that are associated with the highest rate of vancomycin resistance. The introduction of antimicrobial agents with specific activity against vancomycin-resistant Enterococcus (VRE) faecium including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline did not completely resolve this clinical dilemma. In this review, the mechanisms of action and resistance to currently available anti-VRE antimicrobial agents including newer agents such as oritavancin and dalbavancin will be presented. In addition, novel combination therapies including β-lactams and fosfomycin, and the promising results from in vitro, animal studies, and clinical experience in the treatment of VRE faecium will be discussed. © 2017 Pharmacotherapy Publications, Inc.

Use of antibiotics in the management of postirradiation wound infection and sepsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brook, I.

1988-07-01

Ionizing gamma irradiation depresses the host defenses and enhances the susceptibility of the immunocompromised host to local and systemic infection due to endogenous or exogenous microorganisms. Trauma and wounding act synergistically and decrease the survival after exposure to irradiation. The current antimicrobial agents suitable for controlling serious infections and their use in post irradiation local and systemic infection with and without trauma are discussed. The experience gained in managing immunocompromised patients following chemotherapy is reviewed. Empiric single agent or combination agent therapy should be directed at the eradication of potential gram-negative as well as gram-positive pathogens. The most important organismsmore » known to cause these infections are Pseudomonas sp. and Enterobacteriaceae. Management of intra-abdominal infections following trauma should include early surgical correlation and antimicrobials directed against the Bacteroides fragilis group and Enterobacteriaceae. Staphylococcus aureus and Streptococcus pyogenes cause most skin and soft tissue infections following trauma. Chemoprophylaxis of enteric sources of systemic infection can be achieved by antimicrobials that selectively inhibit the Enterobacteriaceae sp. and preserve the anaerobic flora. The management of infection in the injured and irradiated host includes supportive and restorative therapy. Supportive therapy includes debridement and cleansing of wounds, fluids, immunoglobulin, and antimicrobials. Restorative therapy includes definite surgery repair and replenishment of the immune system by use of immunomodulators, growth factors, and bone marrow transplantation. Further studies are needed to examine the usefulness of presently available drugs and experimental agents in the irradiated and traumatized host. 111 references.« less

In Vitro Antimicrobial Photodynamic Therapy Against Trichophyton mentagrophytes Using New Methylene Blue as the Photosensitizer.

PubMed

López-Chicón, P; Gulías, Ò; Nonell, S; Agut, M

2016-11-01

Antimicrobial photodynamic therapy combines the use of a photosensitizing drug with light and oxygen to eradicate pathogens. Trichophyton mentagrophytes is a dermatophytic fungus able to invade the skin and keratinized tissues. We have investigated the use of new methylene blue as the photosensitizing agent for antimicrobial photodynamic therapy to produce the in vitro inactivation of T mentagrophytes. A full factorial design was employed to optimize the parameters for photoinactivation of the dermatophyte. The parameters studied were new methylene blue concentration, contact time between the photosensitizing agent and the fungus prior to light treatment, and the fluence of red light (wavelength, 620-645nm) applied. The minimum concentration of new methylene blue necessary to induce the death of all T. mentagrophytes cells in the initial suspension (approximate concentration, 10 6 colony forming units per milliliter) was 50μM for a fluence of 81J/cm 2 after a contact time of 10minutes with the photosensitizing-agent. Increasing the concentration to 100μM allowed the fluence to be decreased to 9J/cm 2 . Comparison of our data with other published data shows that the susceptibility of T. mentagrophytes to antimicrobial photodynamic therapy with new methylene blue is strain-dependent. New methylene blue is a photosensitizing agent that should be considered for the treatment of fungal skin infections caused by this dermatophyte. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

[Resistance of urinary tract pathogens and the choice of antimicrobial therapy: deceptive simplicity].

PubMed

Rafalskiy, V V; Dovgan, E V

2017-07-01

Urinary tract infection (UTI) is one of the most common reasons for prescribing antibiotics in outpatient and inpatient settings. One of the main criteria for selecting antimicrobial drugs for treating UTI is data on the antibiotic resistance of uropathogens. The article discusses the difficulties in interpreting the results of antimicrobial sensitivity testing of uropathogens and the impact of antibiotic resistance of uropathogens on the clinical effectiveness of managing UTI.

[Neumonía acquired in the community. Practical guide elaborated by a committee intersocieties].

PubMed

Luna, Carlos M; Calmaggi, Aníbal; Caberloto, Oscar; Gentile, Jorge; Valentini, Ricardo; Ciruzzi, Julian; Clara, Liliana; Rizzo, Oscar; Lasdica, Sergio; Blumenfeld, Marcelo; Benchetrit, Guillermo; Famiglietti, Angela; Apezteguia, Carlos; Monteverde, Alfredo

2003-01-01

Clinical practice guidelines for community-acquired pneumonia (CAP) contribute to improve patient's management. CAP undergoes continuous changes in etiology, epidemiology and antimicrobial sensitivity, requiring periodic guidelines revisions. An inter-society committee designed this guidelines dividing it into several topics based on prior guidelines and recent clinical studies. CAP compromises annually more than 1% of the population; most of the cases only require outpatient care but others are severe cases, reaching the 6th cause of death in Argentina. The cases are distributed unevenly into ambulatory, admitted in the general ward or in the intensive care unit. There is no way to predict the etiology. Unfavorable outcome predictors include age, antecedents and physical, laboratory and radiography findings. Ten to 25% of inpatients need to be admitted to the intensive care unit at the onset or during the follow-up, for mechanical ventilation or hemodynamic support (severe CAP). Severe CAP is associated with high mortality and requires adequate and urgent therapy. Pregnant, COPD and nursing home patients require special recommendations. Diagnosis is clinical, while complementary methods are useful to define etiology and severity; chest X-ray is the only one universally recommended. Other studies, including microbiologic evaluation are particularly appropriate in the hospitalized patients. The initial therapy is empiric, it must begin early, using antimicrobials active against the target microorganisms, avoiding their inappropriate use which can lead to the development of resistance. Length of therapy must not be unnecessarily prolonged. Hydratation, nutrition, oxygen and therapy of complications must complement antibiotic treatment. Prevention is based on influenza prophylaxis, anti-pneumococcal vaccine, aspiration prevention and other general measures.

Synergistic combination dry powders for inhaled antimicrobial therapy

NASA Astrophysics Data System (ADS)

Heng, Desmond; Lee, Sie Huey; Teo, Jeanette; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B. H.

2013-06-01

Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI® Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® DPI at 60 L/min. Time-kill studies carried out against common respiratory tract pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Acinetobacter baumannii at 1x the minimum inhibitory concentration (MIC) over 24 hours revealed no antagonistic behavior for both combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the binary combination when it was tested against Pseudomonas aeruginosa bacteria.

Impact of Time to Appropriate Therapy on Mortality in Patients with Vancomycin-Intermediate Staphylococcus aureus Infection

PubMed Central

Warren, David K.; Kollef, Marin H.

2016-01-01

Despite the increasing incidence of vancomycin-intermediate Staphylococcus aureus (VISA) infections, few studies have examined the impact of delay in receipt of appropriate antimicrobial therapy on outcomes in VISA patients. We examined the effects of timing of appropriate antimicrobial therapy in a cohort of patients with sterile-site methicillin-resistant S. aureus (MRSA) and VISA infections. In this single-center, retrospective cohort study, we identified all patients with MRSA or VISA sterile-site infections from June 2009 to February 2015. Clinical outcomes were compared according to MRSA/VISA classification, demographics, comorbidities, and antimicrobial treatment. Thirty-day all-cause mortality was modeled with Kaplan-Meier curves. Multivariate logistic regression analysis (MVLRA) was used to determine odds ratios for mortality. We identified 354 patients with MRSA (n = 267) or VISA (n = 87) sterile-site infection. Fifty-five patients (15.5%) were nonsurvivors. Factors associated with mortality in MVLRA included pneumonia, unknown source of infection, acute physiology and chronic health evaluation (APACHE) II score, solid-organ malignancy, and admission from skilled care facilities. Time to appropriate antimicrobial therapy was not significantly associated with outcome. Presence of a VISA infection compared to that of a non-VISA S. aureus infection did not result in excess mortality. Linezolid use was a risk for mortality in patients with APACHE II scores of ≥14. Our results suggest that empirical vancomycin use in patients with VISA infections does not result in excess mortality. Future studies should (i) include larger numbers of patients with VISA infections to confirm the findings presented here and (ii) determine the optimal antibiotic therapy for critically ill patients with MRSA and VISA infections. PMID:27401565

Antimicrobial susceptibility of clinically isolated anaerobic bacteria in a University Hospital Centre Split, Croatia in 2013.

PubMed

Novak, Anita; Rubic, Zana; Dogas, Varja; Goic-Barisic, Ivana; Radic, Marina; Tonkic, Marija

2015-02-01

Anaerobic bacteria play a significant role in many endogenous polymicrobial infections. Since antimicrobial resistance among anaerobes has increased worldwide, it is useful to provide local susceptibility data to guide empirical therapy. The present study reports recent data on the susceptibility of clinically relevant anaerobes in a University Hospital Centre (UHC) Split, Croatia. A total of 63 Gram-negative and 59 Gram-positive anaerobic clinical isolates from various body sites were consecutively collected from January to December 2013. Antimicrobial susceptibility testing was performed using standardized methods and interpreted using EUCAST criteria. Patient's clinical and demographic data were recorded by clinical microbiologist. Among 35 isolates of Bacteroides spp., 97.1% were resistant to penicillin (PCN), 5.7% to amoxicillin/clavulanic acid (AMC), 8.6% to piperacillin/tazobactam (TZP), 29.0% to clindamycin (CLI) and 2.9% to metronidazole (MZ). Percentages of susceptible strains to imipenem (IPM), meropenem (MEM) and ertapenem (ETP) were 94.3. Resistance of other Gram-negative bacilli was 76.0% to PCN, 8.0% to AMC, 12.0% to TZP, 28.0% to CLI and 8% to MZ. All other Gram-negative strains were fully susceptible to MEM and ETP, while 96.0% were susceptible to IPM. Clostridium spp. isolates were 100% susceptible to all tested antibiotics except to CLI (two of four tested isolates were resistant). Propionibacterium spp. showed resistance to CLI in 4.3%, while 100% were resistant to MZ. Among other Gram-positive bacilli, 18.2% were resistant to PCN, 9.1% to CLI and 54.5% to MZ, while 81.8% of isolates were susceptible to carbapenems. Gram-positive cocci were 100% susceptible to all tested antimicrobials except to MZ, where 28.6% of resistant strains were recorded. Abdomen was the most common source of isolates (82.5%). The most prevalent types of infection were abscess (22.1%), sepsis (14.8%), appendicitis (13.9%) and peritonitis (6.6%). Twenty four patients (19.7%) received empiric antimicrobial therapy. One hundred and one patients (82.8%) had polymicrobial aerobic/anaerobic isolates cultivated from the same specimens. Almost all aerobic bacteria were of endogenous origin and showed fully susceptible antimicrobial profile; only 8.7% (9/104) were multiresistant and considered as hospital acquired. Based on our findings, β-lactam/β-lactamase inhibitor combinations and metronidazole remain useful antimicrobials for empiric treatment of anaerobic infections, while carbapenems should be reserved for situations were multidrug resistant, aerobic or facultative Gram-negative bacteria are expected. However, a certain percentage of resistant isolates were observed for each of these agents. Therefore, periodic resistance surveillance in anaerobes is highly recommended in order to guide empirical therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Community Intervention Model to Reduce Inappropriate Antibiotic Use

ERIC Educational Resources Information Center

Alder, Stephen; Wuthrich, Amy; Haddadin, Bassam; Donnelly, Sharon; Hannah, Elizabeth Lyon; Stoddard, Greg; Benuzillo, Jose; Bateman, Kim; Samore, Matthew

2010-01-01

Background: The Inter-Mountain Project on Antibiotic Resistance and Therapy (IMPART) is an intervention that addresses emerging antimicrobial resistance and the reduction of unnecessary antimicrobial use. Purpose: This study assesses the design and implementation of the community intervention component of IMPART. Methods: The study was conducted…

The design and evaluation of an antimicrobial resistance surveillance system for neonatal intensive care units in Iran.

PubMed

Rezaei-Hachesu, Peyman; Samad-Soltani, Taha; Yaghoubi, Sajad; GhaziSaeedi, Marjan; Mirnia, Kayvan; Masoumi-Asl, Hossein; Safdari, Reza

2018-07-01

Neonatal intensive care units (NICUs) have complex patients in terms of their diagnoses and required treatments. Antimicrobial treatment is a common therapy for patients in NICUs. To solve problems pertaining to empirical therapy, antimicrobial stewardship programs have recently been introduced. Despite the success of these programs in terms of data collection, there is still inefficiency in terms of analyzing and reporting the data. Thus, to successfully implement these stewardship programs, the design of antimicrobial resistance (AMR) surveillance systems is recommended as a first step. As a result, this study aimed to design an AMR surveillance system for use in the NICUs in northwestern Iranian hospitals to cover these information gaps. The recommended system is compatible with the World Health Organization (WHO) guidelines. The business intelligence (BI) requirements were extracted in an interview with a product owner (PO) using a valid and reliable checklist. Following this, an AMR surveillance system was designed and evaluated in relation to user experiences via a user experience questionnaire (UEQ). Finally, an association analysis was performed on the database, and the results were reported by identifying the important multidrug resistances in the database. A customized software development methodology was proposed. The three major modules of the AMR surveillance are the data registry, dashboard, and decision support modules. The data registry module was implemented based on a three-tier architecture, and the Clinical Decision Support System (CDSS) and dashboard modules were designed based on the BI requirements of the Scrum product owner (PO). The mean values of UEQ measures were in a good range. This measures showed the suitable usability of the AMR surveillance system. Applying efficient software development methodologies allows for the systems' compatibility with users' opinions and requirements. In addition, the construction of interdisciplinary communication models for research and software engineering allows for research and development concepts to be used in operational environments. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of a disease state management guideline for urinary tract infection.

PubMed

Zmarlicka, Monika T; Cardwell, Sophia M; Crandon, Jared L; Nicolau, David P; McClure, Mitchell H; Nailor, Michael D

2016-06-01

A urinary tract infection (UTI) disease state management guideline, including risk-based antimicrobial recommendations, Foley catheter management and transitions of care, was implemented. This study evaluated the outcomes associated with implementation of the guideline. A retrospective study was conducted between 1 July 2013 and 30 September 2013 (pre-implementation) and between 1 July 2014 and 30 September 2014 (post-implementation). Symptomatic patients treated for UTI within 24 h with an identified pathogen were included. Risk-based patient groups were community-acquired UTI, healthcare-associated UTI, or extended-spectrum β-lactamase (ESBL) history in prior 12 months. Recommended antimicrobials were ceftriaxone, cefepime ± vancomycin, or doripenem ± vancomycin, respectively. Given the low post-implementation guideline adherence, pre- and post-groups were combined to evaluate potential guideline value. Length of stay (LOS) decreased when guidelines were followed [5 (IQR 4-7) days vs. 6 (IQR 4-8) days; P = 0.03] or appropriate therapy (according to in vitro susceptibilities) was given [5 (IQR 4-7) days vs. 6 (IQR 4-9) days; P = 0.03]. Those receiving guideline-recommended antimicrobials were more likely to have appropriate therapy within 24 h (84.4% vs. 64.2%; P <0.001). On multivariate analysis, intensive care unit (ICU) admission and admission from home were associated with longer and shorter LOS, respectively. Despite less than anticipated adherence, these data suggest that the established disease state management guideline can improve outcomes in patients admitted with UTI. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Reducing Antimicrobial Usage in Pig Production without Jeopardizing Production Parameters.

PubMed

Postma, M; Vanderhaeghen, W; Sarrazin, S; Maes, D; Dewulf, J

2017-02-01

Antimicrobial usage (AMU) has been described to be high in pig production. Although farmers are aware of the high usage, little is known about intervention to improve the situation. This study evaluated the extent to which AMU could be reduced in pig production by the optimization of herd management, biosecurity status, vaccination strategy, anthelmintic therapy and advice on prudent AMU. Furthermore, the effects of these interventions on the herd production results were explored. This intervention study was conducted on 61 Flemish pig herds and included three visits per herd. During the initial visit, information was gathered on herd management, biosecurity status (quantified by means of the Biocheck.UGent ™ risk-based scoring system), vaccination strategy, anthelmintic therapy and AMU. This info was then translated into a herd-specific action plan which was discussed with the farmer and herd veterinarian/other advisors during the second visit. In the final herd visit (±8 months later), comparable data were obtained to evaluate the progress. Overall, a significant improvement of 2.4 points external and 7 points internal biosecurity on the herds was obtained, combined with additional vaccination, anthelmintic therapy and prudent AMU. This was accompanied by a significant reduction in the AMU with a decrease of 52% for the pigs from birth till slaughter and 32% for breeding animals, based on treatment incidences (TIs) and included an important reduction in the use of critically important antimicrobials. More importantly, the increased biosecurity levels and decreased AMU were combined with significantly improved technical results such as the number of weaned piglets per sow per year (+1.1), daily weight gain (+5.9 g/day) and mortality in the finisher period (-0.6%). Guided interventions as a team effort of farmer and herd veterinarian/other advisors have shown to be a promising method in the reduction of AMU in pig production. © 2016 Blackwell Verlag GmbH.

A systematic review of clinical decision support systems for antimicrobial management: are we failing to investigate these interventions appropriately?

PubMed

Rawson, T M; Moore, L S P; Hernandez, B; Charani, E; Castro-Sanchez, E; Herrero, P; Hayhoe, B; Hope, W; Georgiou, P; Holmes, A H

2017-08-01

Clinical decision support systems (CDSS) for antimicrobial management can support clinicians to optimize antimicrobial therapy. We reviewed all original literature (qualitative and quantitative) to understand the current scope of CDSS for antimicrobial management and analyse existing methods used to evaluate and report such systems. PRISMA guidelines were followed. Medline, EMBASE, HMIC Health and Management and Global Health databases were searched from 1 January 1980 to 31 October 2015. All primary research studies describing CDSS for antimicrobial management in adults in primary or secondary care were included. For qualitative studies, thematic synthesis was performed. Quality was assessed using Integrated quality Criteria for the Review Of Multiple Study designs (ICROMS) criteria. CDSS reporting was assessed against a reporting framework for behaviour change intervention implementation. Fifty-eight original articles were included describing 38 independent CDSS. The majority of systems target antimicrobial prescribing (29/38;76%), are platforms integrated with electronic medical records (28/38;74%), and have a rules-based infrastructure providing decision support (29/38;76%). On evaluation against the intervention reporting framework, CDSS studies fail to report consideration of the non-expert, end-user workflow. They have narrow focus, such as antimicrobial selection, and use proxy outcome measures. Engagement with CDSS by clinicians was poor. Greater consideration of the factors that drive non-expert decision making must be considered when designing CDSS interventions. Future work must aim to expand CDSS beyond simply selecting appropriate antimicrobials with clear and systematic reporting frameworks for CDSS interventions developed to address current gaps identified in the reporting of evidence. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human antimicrobial peptides LL-37 and human β-defensin-2 reduce viral replication in keratinocytes infected with varicella zoster virus.

PubMed

Crack, L R; Jones, L; Malavige, G N; Patel, V; Ogg, G S

2012-07-01

There is mounting evidence that antimicrobial peptides have an important role in cutaneous defence, but the expression of these antimicrobial peptides in atopic eczema (AE) is still unclear. There are several families of antimicrobial peptides, including cathelicidins and human β-defensins. Patients with AE are more susceptible to severe cutaneous viral infections, including varicella zoster virus (VZV). To characterize the functional activity of the antimicrobial peptides LL-37 (human cathelicidin) and human β-defensin (hBD)-2 keratinocytes were infected with VZV, in a skin-infection model. Flow-cytometry analysis was used to investigate LL-37 expression in normal human keratinocytes, and quantitative PCR was used to determine viral loads in infected HaCaT keratinocytes and B cells, with and without exogenous LL-37 and hBD-2. LL-37 expression was present in keratinocytes, and both exogenous LL-37 and hBD-2 significantly reduced VZV load in infected keratinocytes and B cells. Specific antibodies blocked the antiviral action exhibited by these antimicrobial peptides. Pre-incubation of VZV with LL-37, but not hBD-2, further reduced VZV load. Both LL-37 and hBD-2 have an antiviral effect on VZV replication in the keratinocyte HaCaT cell line and in B cells, but their mechanism of action is different. Evidence of the relationship between antimicrobial peptide expression and higher susceptibility to infections in AE skin is still emerging. Developing novel antiviral therapies based on antimicrobial peptides may provide improved treatment options for patients with AE. © The Author(s). CED © 2012 British Association of Dermatologists.

Molecular Antimicrobial Resistance Surveillance for Neisseria gonorrhoeae, Northern Territory, Australia.

PubMed

Whiley, David M; Trembizki, Ella; Buckley, Cameron; Freeman, Kevin; Baird, Robert W; Beaman, Miles; Chen, Marcus; Donovan, Basil; Kundu, Ratan L; Fairley, Christopher K; Guy, Rebecca; Hogan, Tiffany; Kaldor, John M; Karimi, Mahdad; Limnios, Athena; Regan, David G; Ryder, Nathan; Su, Jiunn-Yih; Ward, James; Lahra, Monica M

2017-09-01

Neisseria gonorrhoeae antimicrobial resistance (AMR) is a globally recognized health threat; new strategies are needed to enhance AMR surveillance. The Northern Territory of Australia is unique in that 2 different first-line therapies, based primarily on geographic location, are used for gonorrhea treatment. We tested 1,629 N. gonorrhoeae nucleic acid amplification test-positive clinical samples, collected from regions where ceftriaxone plus azithromycin or amoxicillin plus azithromycin are recommended first-line treatments, by using 8 N. gonorrhoeae AMR PCR assays. We compared results with those from routine culture-based surveillance data. PCR data confirmed an absence of ceftriaxone resistance and a low level of azithromycin resistance (0.2%), and that penicillin resistance was <5% in amoxicillin plus azithromycin regions. Rates of ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae were lower when molecular methods were used. Molecular methods to detect N. gonorrhoeae AMR can increase the evidence base for treatment guidelines, particularly in settings where culture-based surveillance is limited.

What are the similarities and differences in antimicrobial prescribing between Australian public and private hospitals?

PubMed

Cotta, M O; Chen, C; Tacey, M; James, R S; Buising, K L; Marshall, C; Thursky, K A

2016-10-01

Identifying themes associated with inappropriate prescribing in Australian public and private hospitals will help target future antimicrobial stewardship initiatives. To describe current antimicrobial prescribing practices, identify similarities and differences between hospital sectors and provide target areas for improvement specific to each hospital sector. All hospitals included in the study were part of the 2014 national antimicrobial prescribing survey and conducted one of the following: a whole hospital point prevalence survey, serial point prevalence surveys or a sample of randomly selected patients. Data on the types of antibiotics used, their indications for use and the quality of prescription based on compliance with national and local prescribing guidelines were collected. Two hundred and two hospitals (166 public and 36 private) comprising 10 882 patients and 15 967 antimicrobial prescriptions were included. Public hospitals had higher proportions of prescriptions for treatment (81.5% vs 48.4%) and medical prophylaxis (8.8% and 4.6%), whilst private hospitals had significantly higher surgical prophylaxis use (9.6% vs 46.9%) (P < 0.001). In public hospitals, the main reasons for non-compliance of treatment prescriptions were spectrum being too broad (30.5%) while in private it was incorrect dosing. Prolonged duration was the main reason for non-compliance among surgical prophylaxis prescriptions in both types of hospitals. Australian hospitals need to target specific areas to improve antimicrobial use. Specifically, unnecessary broad-spectrum therapy should be a priority area in public hospitals, whilst emphasis on curtailing antimicrobial overuse in surgical prophylaxis needs to be urgently addressed across in the private hospital sector. © 2016 Royal Australasian College of Physicians.

Pharmacist-driven antimicrobial optimization in the emergency department.

PubMed

Davis, Lucretia C; Covey, Robin B; Weston, Jaye S; Hu, Bee Bee Y; Laine, Gregory A

2016-03-01

A pharmacist-driven antimicrobial optimization service in the non-trauma emergency department (ED) of an 864-bed non-profit tertiary care teaching hospital was reviewed to assess its value. Local antimicrobial resistance patterns of urine, wound, stool, and blood cultures were also studied to determine whether or not empiric prescribing practices should be modified. A retrospective electronic chart review was performed for ED patients with positive cultures during two different three-month periods. During Period 1, ED nursing management performed positive culture follow-up. During Period 2, ED clinical pharmacists performed this role. The primary objective was to determine the value of the pharmacist-driven antimicrobial optimization service as measured by the number of clinical interventions made when indicated. The secondary objective was to examine resistance patterns of urine and wound isolates in order to determine if empiric prescribing patterns in the ED should be modified. During Period 1, there were 499 patient visits with subsequent positive cultures. Of those, 76 patients (15%) were discharged home. Nursing management intervened on 21 of 42 (50%) positive cultures that required an intervention; in Period 2, there were 473 patient visits with subsequent positive cultures, and 64 (14%) were discharged home. Pharmacists intervened on 24 of 30 (80%) cultures where an intervention was indicated resulting in a 30% increase in interventions for inappropriate therapy (p = 0.01). A review of the secondary objective revealed a 38% fluoroquinolone resistance rate of E. coli, the most frequently isolated urinary organism. Pharmacist-driven antimicrobial stewardship program resulted in a 30% absolute increase in interventions for inappropriate therapy as compared to the nursing-driven model. This stewardship program has further demonstrated the value of ED pharmacists. Pharmacist interventions should help to ensure that infections are resolved through modification of antimicrobial therapies for patients with bug-drug mismatches. The fluoroquinolone resistance rate indicates a need to consider alternative therapies for uncomplicated urinary tract infections. Nitrofurantoin remains with good coverage against E. coli and Enterococcus species but should be used in uncomplicated patients with normal renal function. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Current and future treatment options for gonorrhoea.

PubMed

Ison, Catherine A; Deal, Carolyn; Unemo, Magnus

2013-12-01

The delivery of effective antimicrobial therapy is essential for public health control of gonorrhoea, in the absence of a suitable vaccine. The antimicrobial agent chosen should have high efficacy and quality, lack toxicity and give >95% success when given empirically. Guidelines, which are informed by surveillance data, are used to aid clinicians in their choice of appropriate agent. Historically, gonorrhoea treatment has been delivered as a single, directly observed dose but this has resulted in failure of successive antimicrobial agents which have been replaced by a new antimicrobial to which resistance has been rare or non-existing. Following the drift towards decreased susceptibility and treatment failure to the extended spectrum cephalosporins, and the lack of 'new' alternative antimicrobials, the threat of difficult to treat or untreatable gonorrhoea has emerged. The challenge of maintaining gonorrhoea as a treatable infection has resulted in national, regional and global response or action plans. This review discusses different approaches to the future treatment of gonorrhoea including; use of ceftriaxone, the injectable cephalosporin at increased dosage; dual antimicrobial therapy; use of drugs developed for other infections and use of older agents, directed by rapid point of care tests, to susceptible infections. Finally, it is considered whether the time is right to readdress the possibility of developing an effective gonococcal vaccine, given the major advances in our understanding of natural infection, molecular pathogenesis and the revolution in molecular biology techniques.

Antibiotic resistance and biofilm tolerance: a combined threat in the treatment of chronic infections.

PubMed

Bowler, Philip G

2018-05-02

Since the introduction of antibiotics into human medicine in the 1940's, antibiotic resistance has emerged at an alarming rate and is now a major threat to public health. This problem is amplified by pathogenic bacteria existing most commonly in biofilm form, creating additional bacterial tolerance to antimicrobial agents. Biofilm is now considered to be a primary cause of chronic infection, and antibiotic-resistant bacteria are prevalent in biofilm form. In particular, chronic non-healing wounds commonly harbour complex polymicrobial, pathogenic biofilm that is tolerant to systemic and topical antimicrobial therapy. Antibiotic stewardship programmes have emerged globally to improve antibiotic prescribing practices, and to curb the emergence and spread of bacterial resistance. In this regard, new antimicrobial strategies must be considered, one of which is to use antibiofilm/antimicrobial combinations to disrupt biofilm, thereby facilitating effectiveness of antimicrobial agents, and reducing the opportunity for antibiotic resistance gene transfer within biofilm. This strategy is being considered in several clinical conditions, one of which is chronic non-healing wounds, where antibiotics are used excessively and often indiscriminately. A combination antibiofilm/antimicrobial wound dressing has been shown to facilitate healing in previously biofilm-impaired non-healing wounds. This approach must be considered as part of antibiotic stewardship programmes to reduce the usage and implications of antibiotic therapy, and improve outcomes associated with chronic infections.

Burden of laboratory-confirmed Campylobacter infections in Guatemala 2008–2012: Results from a facility-based surveillance system

PubMed Central

Benoit, Stephen R.; Lopez, Beatriz; Arvelo, Wences; Henao, Olga; Parsons, Michele B.; Reyes, Lissette; Moir, Juan Carlos; Lindblade, Kim

2015-01-01

Introduction Campylobacteriosis is one of the leading causes of gastroenteritis worldwide. This study describes the epidemiology of laboratory-confirmed Campylobacter diarrheal infections in two facility-based surveillance sites in Guatemala. Methods Clinical, epidemiologic, and laboratory data were collected on patients presenting with acute diarrhea from select healthcare facilities in the departments of Santa Rosa and Quetzaltenango, Guatemala, from January 2008 through August 2012. Stool specimens were cultured for Campylobacter and antimicrobial susceptibility testing was performed on a subset of isolates. Multidrug resistance (MDR) was defined as resistance to ≥3 antimicrobial classes. Results Campylobacter was isolated from 306 (6.0%) of 5137 stool specimens collected. For children <5 years of age, annual incidence was as high as 1288.8 per 100,000 children in Santa Rosa and 185.5 per 100,000 children in Quetzaltenango. Among 224 ambulatory care patients with Campylobacter, 169 (75.5%) received metronidazole or trimethoprim-sulfamethoxazole, and 152 (66.7%) received or were prescribed oral rehydration therapy. Antimicrobial susceptibilities were tested in 96 isolates; 57 (59.4%) were resistant to ciprofloxacin and 12 (12.5%) were MDR. Conclusion Campylobacter was a major cause of diarrhea in children in two departments in Guatemala; antimicrobial resistance was high, and treatment regimens in the ambulatory setting which included metronidazole and trimethoprim-sulfamethoxazole and lacked oral rehydration were sub-optimal. PMID:24534336

Burden of laboratory-confirmed Campylobacter infections in Guatemala 2008-2012: results from a facility-based surveillance system.

PubMed

Benoit, Stephen R; Lopez, Beatriz; Arvelo, Wences; Henao, Olga; Parsons, Michele B; Reyes, Lissette; Moir, Juan Carlos; Lindblade, Kim

2014-03-01

Campylobacteriosis is one of the leading causes of gastroenteritis worldwide. This study describes the epidemiology of laboratory-confirmed Campylobacter diarrheal infections in two facility-based surveillance sites in Guatemala. Clinical, epidemiologic, and laboratory data were collected on patients presenting with acute diarrhea from select healthcare facilities in the departments of Santa Rosa and Quetzaltenango, Guatemala, from January 2008 through August 2012. Stool specimens were cultured for Campylobacter and antimicrobial susceptibility testing was performed on a subset of isolates. Multidrug resistance (MDR) was defined as resistance to ≥3 antimicrobial classes. Campylobacter was isolated from 306 (6.0%) of 5137 stool specimens collected. For children <5 years of age, annual incidence was as high as 1288.8 per 100,000 children in Santa Rosa and 185.5 per 100,000 children in Quetzaltenango. Among 224 ambulatory care patients with Campylobacter, 169 (75.5%) received metronidazole or trimethoprim-sulfamethoxazole, and 152 (66.7%) received or were prescribed oral rehydration therapy. Antimicrobial susceptibilities were tested in 96 isolates; 57 (59.4%) were resistant to ciprofloxacin and 12 (12.5%) were MDR. Campylobacter was a major cause of diarrhea in children in two departments in Guatemala; antimicrobial resistance was high, and treatment regimens in the ambulatory setting which included metronidazole and trimethoprim-sulfamethoxazole and lacked oral rehydration were sub-optimal. Published by Elsevier Ltd.

Differences in antimicrobial consumption, prescribing and isolation rate of multidrug resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii on surgical and medical wards

PubMed Central

Scepanovic, Radisav; Vitorovic, Teodora; Novakovic, Radmila; Milanov, Nenad; Bukumiric, Zoran; Carevic, Biljana; Trajkovic, Jasmina; Rajkovic, Jovana

2017-01-01

In order to provide guidance data for clinically rational use of an antibiotics consuption, prescribing and prevalence of multidrug resistant (MDR) Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii were monitored on the surgical (S) and medical (M) wards of the University Hospital Center “Dr. Dragisa Misovic-Dedinje” (Belgrade, Serbia), in the study period from 2012 to 2015. Appropriateness of antimicrobial use was evaluated using the Global-Prevalence Survey method designed by the University of Antwerp. The percentages of MDR pathogens relative to the total number of isolates of K. pneumoniae and P. aeruginosa were higher on the S (86.2% and 49.1%) than on the M (63.2% and 36.9%) wards. The percentage of MDR A. baumannii was not different between S (93.7%) and M (79.5%) wards. An overall antibiotics consumption (defined daily doses/100 bed-days) during study was 369.7 and 261.5 on the S and M wards, respectively. A total of 225 prescriptions of antimicrobials were evaluated in138 adults admitted to wards on the day of the survey. The percentage of antimicrobials prescribed for prophylaxis on the M and S wards were 0% and 25%, respectively. Therapies were more frequently empiric (S, 86.8% and M, 80%). The percentages of medical errors on the S and M wards were 74.6% and 27.3%, respectively. The quality indicators for antibiotic prescribing on the S and M wards were as follows: the incorrect choice of antimicrobials (35.6% vs. 20.0%), inappropriate dose interval (70.6% vs. 16.9%) or duration of therapy (72.5% vs. 23.1%), a non-documented stop/review data (73.6% vs. 16.9%) and divergence from guidelines (71.9% vs. 23.1%). Treatment based on biomarkers was more common on the M wards as compared to the S wards. The increasing prevalence of MDR pathogens, a very high consumption and incorrect prescribing of antimicrobials need special attention, particularly on the S wards. PMID:28467437

Differences in antimicrobial consumption, prescribing and isolation rate of multidrug resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii on surgical and medical wards.

PubMed

Zivanovic, Vladimir; Gojkovic-Bukarica, Ljiljana; Scepanovic, Radisav; Vitorovic, Teodora; Novakovic, Radmila; Milanov, Nenad; Bukumiric, Zoran; Carevic, Biljana; Trajkovic, Jasmina; Rajkovic, Jovana; Djokic, Vladimir

2017-01-01

In order to provide guidance data for clinically rational use of an antibiotics consuption, prescribing and prevalence of multidrug resistant (MDR) Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii were monitored on the surgical (S) and medical (M) wards of the University Hospital Center "Dr. Dragisa Misovic-Dedinje" (Belgrade, Serbia), in the study period from 2012 to 2015. Appropriateness of antimicrobial use was evaluated using the Global-Prevalence Survey method designed by the University of Antwerp. The percentages of MDR pathogens relative to the total number of isolates of K. pneumoniae and P. aeruginosa were higher on the S (86.2% and 49.1%) than on the M (63.2% and 36.9%) wards. The percentage of MDR A. baumannii was not different between S (93.7%) and M (79.5%) wards. An overall antibiotics consumption (defined daily doses/100 bed-days) during study was 369.7 and 261.5 on the S and M wards, respectively. A total of 225 prescriptions of antimicrobials were evaluated in138 adults admitted to wards on the day of the survey. The percentage of antimicrobials prescribed for prophylaxis on the M and S wards were 0% and 25%, respectively. Therapies were more frequently empiric (S, 86.8% and M, 80%). The percentages of medical errors on the S and M wards were 74.6% and 27.3%, respectively. The quality indicators for antibiotic prescribing on the S and M wards were as follows: the incorrect choice of antimicrobials (35.6% vs. 20.0%), inappropriate dose interval (70.6% vs. 16.9%) or duration of therapy (72.5% vs. 23.1%), a non-documented stop/review data (73.6% vs. 16.9%) and divergence from guidelines (71.9% vs. 23.1%). Treatment based on biomarkers was more common on the M wards as compared to the S wards. The increasing prevalence of MDR pathogens, a very high consumption and incorrect prescribing of antimicrobials need special attention, particularly on the S wards.

Mastitis therapy and antimicrobial susceptibility: a multispecies review with a focus on antibiotic treatment of mastitis in dairy cattle.

PubMed

Barlow, John

2011-12-01

Mastitis occurs in numerous species. Antimicrobial agents are used for treatment of infectious mastitis in dairy cattle, other livestock, companion animals, and humans. Mastitis is an economically important disease of dairy cattle and most mastitis research has focused on epidemiology and control of bovine mastitis. Antibiotic treatment of clinical and subclinical mastitis in dairy cattle is an established component of mastitis control programs. Research on the treatment of clinical and subclinical mastitis in other dairy species such as sheep and goats has been less frequent, although the general principles of mastitis therapy in small ruminants are similar to those of dairy cattle. Research on treatment of clinical mastitis in humans is limited and as for other species empirical treatment of mastitis appears to be common. While antimicrobial susceptibility testing is recommended to direct treatment decisions in many clinical settings, the use of susceptibility testing for antibiotic selection for mastitis treatments of dairy cattle has been challenged in a number of publications. The principle objective of this review is to summarize the literature evaluating the question, "Does antimicrobial susceptibility predict treatment outcome for intramammary infections caused by common bacterial pathogens?" This review also addresses current issues related to antimicrobial use and treatment decisions for mastitis in dairy cattle. Information on treatment of mastitis in other species, including humans, is included although research appears to be limited. Issues related to study design, gaps in current knowledge and opportunities for future research are identified for bovine mastitis therapy.

Antimicrobial Resistance in Asia: Current Epidemiology and Clinical Implications

PubMed Central

Kang, Cheol-In

2013-01-01

Antimicrobial resistance has become one of the most serious public health concerns worldwide. Although circumstances may vary by region or country, it is clear that some Asian countries are epicenters of resistance, having seen rapid increases in the prevalence of antimicrobial resistance of major bacterial pathogens. In these locations, however, the public health infrastructure to combat this problem is very poor. The prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA), macrolide-resistant Streptococcus pneumoniae, and multidrug-resistant enteric pathogens are very high due to the recent emergence of extremely drug-resistant gram-negative bacilli in Asia. Because antimicrobial options for these pathogens are extremely limited, infections caused by antimicrobial-resistant bacteria are often associated with inappropriate antimicrobial therapy and poor clinical outcomes. Physicians should be aware of the current epidemiological status of resistance and understand the appropriate use of antimicrobial agents in clinical practice. This review focuses on describing the epidemiology and clinical implications of antimicrobial-resistant bacterial infections in Asian countries. PMID:24265947

Effects of Menthol Supplementation in Feedlot Cattle Diets on the Fecal Prevalence of Antimicrobial-Resistant Escherichia coli

PubMed Central

Aperce, C. C.; Amachawadi, R.; Van Bibber-Krueger, C. L.; Nagaraja, T. G.; Scott, H. M.; Vinasco-Torre, J.; Drouillard, J. S.

2016-01-01

The pool of antimicrobial resistance determinants in the environment and in the gut flora of cattle is a serious public health concern. In addition to being a source of human exposure, these bacteria can transfer antibiotic resistance determinants to pathogenic bacteria and endanger the future of antimicrobial therapy. The occurrence of antimicrobial resistance genes on mobile genetic elements, such as plasmids, facilitates spread of resistance. Recent work has shown in vitro anti-plasmid activity of menthol, a plant-based compound with the potential to be used as a feed additive to beneficially alter ruminal fermentation. The present study aimed to determine if menthol supplementation in diets of feedlot cattle decreases the prevalence of multidrug-resistant bacteria in feces. Menthol was included in diets of steers at 0.3% of diet dry matter. Fecal samples were collected weekly for 4 weeks and analyzed for total coliforms counts, antimicrobial susceptibilities, and the prevalence of tet genes in E. coli isolates. Results revealed no effect of menthol supplementation on total coliforms counts or prevalence of E. coli resistant to amoxicillin, ampicillin, azithromycin, cefoxitin, ceftiofur, ceftriaxone, chloramphenicol, ciprofloxacin, gentamicin, kanamycin, nalidixic acid, streptomycin, sulfisoxazole, and sulfamethoxazole; however, 30 days of menthol addition to steer diets increased the prevalence of tetracycline-resistant E. coli (P < 0.02). Although the mechanism by which menthol exerts its effects remains unclear, results of our study suggest that menthol may have an impact on antimicrobial resistance in gut bacteria. PMID:28030622

The intrinsic antimicrobial activity of citric acid-coated manganese ferrite nanoparticles is enhanced after conjugation with the antifungal peptide Cm-p5

PubMed Central

Lopez-Abarrategui, Carlos; Figueroa-Espi, Viviana; Lugo-Alvarez, Maria B; Pereira, Caroline D; Garay, Hilda; Barbosa, João ARG; Falcão, Rosana; Jiménez-Hernández, Linnavel; Estévez-Hernández, Osvaldo; Reguera, Edilso; Franco, Octavio L; Dias, Simoni C; Otero-Gonzalez, Anselmo J

2016-01-01

Diseases caused by bacterial and fungal pathogens are among the major health problems in the world. Newer antimicrobial therapies based on novel molecules urgently need to be developed, and this includes the antimicrobial peptides. In spite of the potential of antimicrobial peptides, very few of them were able to be successfully developed into therapeutics. The major problems they present are molecule stability, toxicity in host cells, and production costs. A novel strategy to overcome these obstacles is conjugation to nanomaterial preparations. The antimicrobial activity of different types of nanoparticles has been previously demonstrated. Specifically, magnetic nanoparticles have been widely studied in biomedicine due to their physicochemical properties. The citric acid-modified manganese ferrite nanoparticles used in this study were characterized by high-resolution transmission electron microscopy, which confirmed the formation of nanocrystals of approximately 5 nm diameter. These nanoparticles were able to inhibit Candida albicans growth in vitro. The minimal inhibitory concentration was 250 µg/mL. However, the nanoparticles were not capable of inhibiting Gram-negative bacteria (Escherichia coli) or Gram-positive bacteria (Staphylococcus aureus). Finally, an antifungal peptide (Cm-p5) from the sea animal Cenchritis muricatus (Gastropoda: Littorinidae) was conjugated to the modified manganese ferrite nanoparticles. The antifungal activity of the conjugated nanoparticles was higher than their bulk counterparts, showing a minimal inhibitory concentration of 100 µg/mL. This conjugate proved to be nontoxic to a macrophage cell line at concentrations that showed antimicrobial activity. PMID:27563243

The use of national-level data to describe trends in intramammary antimicrobial usage on Irish dairy farms from 2003 to 2015.

PubMed

More, Simon J; Clegg, Tracy A; McCoy, Finola

2017-08-01

In this study, we used national-level data to describe trends in on-farm intramammary antimicrobial usage in Ireland from 2003 to 2015. We calculated actual sales of intramammary tubes and the quantity of active substance sold, by year, product type [lactation or dry cow therapy (DCT)], antimicrobial group, World Health Organization antimicrobial classification, and from 2009 to 2015, prescribing route. We also estimated on-farm usage of lactation and dry cow intramammary antimicrobials using defined daily dose (DDDvet) and defined course dose (DCDvet) calculations, and dry cow coverage. Sales of tubes of antimicrobial for DCT have increased, and the estimated national dry cow coverage in 2015 was 1,022 DCDvet per 1,000 cows per year. An increase has also occurred in sales of teat sealant (2015 sales: 66.7 tubes with teat sealant for every 100 tubes with antimicrobial for DCT). In contrast, the number of tubes of antimicrobial sold for lactation use has decreased to 1,398 DDDvet and 466 DCDvet per 1,000 animals per year. Sales in intramammary tubes with at least one critically important antimicrobial (CIA) have either risen since 2007 (DCT) or fallen (lactation therapy). Increases were observed in both the number of dry cow and lactation tubes containing CIA considered of highest priority for human health. Differences between prescribing routes with respect to CIA usage were observed. This study provides detailed insight into on-farm usage of intramammary antimicrobials in Ireland. It demonstrates positive national progress but also highlights areas for review. In particular, blanket dry cow treatment in Ireland should be reconsidered. It is not possible to investigate farm-level variation in antimicrobial usage from national sales data. In several countries, measurement and benchmarking have been critical to progress in reducing antimicrobial usage in farm animal production. Central collation of data on farm-level antimicrobial use is also needed in Ireland to allow objective measurement and benchmarking of on-farm usage. More generally, standardized indicators to quantify antimicrobial usage in farm animals are urgently needed to allow country-level comparisons. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

The analysis of the antibiotic resistome offers new opportunities for therapeutic intervention.

PubMed

Corona, Fernando; Blanco, Paula; Alcalde-Rico, Manuel; Hernando-Amado, Sara; Lira, Felipe; Bernardini, Alejandra; Sánchez, María B; Martínez, José L

2016-06-01

Most efforts in the development of antimicrobials have focused on the screening of lethal targets. Nevertheless, the constant expansion of antimicrobial resistance makes the antibiotic resistance determinants themselves suitable targets for finding inhibitors to be used in combination with antibiotics. Among them, inhibitors of antibiotic inactivating enzymes and of multidrug efflux pumps are suitable candidates for improving the efficacy of antibiotics. In addition, the application of systems biology tools is helping to understand the changes in bacterial physiology associated to the acquisition of resistance, including the increased susceptibility to other antibiotics displayed by some antibiotic-resistant mutants. This information is useful for implementing novel strategies based in metabolic interventions or combination of antibiotics for improving the efficacy of antibacterial therapy.

Consensus summary of aerosolized antimicrobial agents: application of guideline criteria. Insights from the Society of Infectious Diseases Pharmacists.

PubMed

Le, Jennifer; Ashley, Elizabeth Dodds; Neuhauser, Melinda M; Brown, Jack; Gentry, Chris; Klepser, Michael E; Marr, Ann Marie; Schiller, Daryl; Schwiesow, Joshua N; Tice, Sally; VandenBussche, Heather L; Wood, G Christopher

2010-06-01

Aerosolized delivery of antimicrobial agents is an attractive option for management of pulmonary infections, as this is an ideal method of providing high local drug concentrations while minimizing systemic exposure. With the paucity of consensus regarding the safety, efficacy, and means with which to use aerosolized antimicrobials, a task force was created by the Society of Infectious Diseases Pharmacists to critically review and evaluate the literature on the use of aerosolized antiinfective agents. This article summarizes key findings and statements for preventing or treating a variety of infectious diseases, including cystic fibrosis, bronchiecstasis, hospital-acquired pneumonia, fungal infections, nontuberculosis mycobacterial infection, and Pneumocystis jiroveci pneumonia. Our intention was to provide guidance for clinicians on the use of aerosolized antibiotics through evidence-based pharmacotherapy. Further research with well-designed clinical trials is necessary to elucidate the optimal dosage and duration of therapy and, of equal importance, to appreciate the true risks associated with the use of aerosolized delivery systems.

Mastitis treatment-Reduction in antibiotic usage in dairy cows.

PubMed

Krömker, V; Leimbach, S

2017-08-01

Animal-friendly, economical, resource-saving milk production provides the basis for sustained consumer acceptance. Bovine mastitis plays a decisive role in the dairy industry-disturbing animal health and welfare and causing considerable economic losses on the other hand. Currently, antimicrobial treatment is indispensable to keep bovine udder health, animal welfare and economic aspects in balance. On the contrary, emergence and spread of antimicrobial resistance (AMR) is an urgent matter of particular public interest, and as a consequence, antimicrobial usage (AMU) in production livestock is a critically discussed subject. In urgent need of future reduction in AMU in the dairy industry, this review article describes and discusses possible approaches promising prompt implementation, including therapeutical alternatives as well as pro- and metaphylactic concepts such as the implementation of evidence-based mastitis therapy concepts and selective dry cow treatment (sDCT), in search of the most effective and contemporary methods for decreasing AMU and AMR in dairy production. © 2017 Blackwell Verlag GmbH.

Review of antimicrobial therapy of selected bacterial diseases in broiler chickens in Canada

PubMed Central

Agunos, Agnes; Léger, Dave; Carson, Carolee

2012-01-01

This paper reviews common therapeutic applications of antimicrobials in broiler chicken production in relation to Canadian guidelines, surveillance data, and emerging public health concerns about antimicrobial use (AMU). Escherichia coli, Clostridium perfringens, and Staphylococcus spp., were reviewed because of their animal health and economic significance. Enterococcus cecorum and Salmonella were included because of their importance in antimicrobial resistance (AMR) surveillance. This review identified that i) antimicrobials are available in Canada to treat infections by these agents, but may be through over the counter or extra-label use, ii) prevalence rates for these diseases are unknown, iii) antimicrobial use estimates in broilers are lacking, and iv) AMR has emerged in clinical isolates, though data are very sparse. This review highlights the need for surveillance of AMU and AMR in broiler chickens in Canada. PMID:23729827

Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions

PubMed Central

Turapov, Obolbek; Waddell, Simon J.; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A.; Tudo, Griselda; Labesse, Gilles; Young, Danielle I.; Young, Michael; Andrew, Peter W.; Butcher, Philip D.; Cohen-Gonsaud, Martin

2014-01-01

Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis. PMID:24590482

Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice

PubMed Central

Elliott, Thomas B.; Bolduc, David L.; Ledney, G. David; Kiang, Juliann G.; Fatanmi, Oluseyi O.; Wise, Stephen Y.; Romaine, Patricia L. P.; Newman, Victoria L.; Singh, Vijay K.

2015-01-01

Purpose: A combination therapy for combined injury (CI) using a non-specific immunomodulator, synthetic trehalose dicorynomycolate and monophosphoryl lipid A (STDCM-MPL), was evaluated to augment oral antimicrobial agents, levofloxacin (LVX) and amoxicillin (AMX), to eliminate endogenous sepsis and modulate cytokine production. Materials and methods: Female B6D2F1/J mice received 9.75 Gy cobalt-60 gamma-radiation and wound. Bacteria were isolated and identified in three tissues. Incidence of bacteria and cytokines were compared between treatment groups. Results: Results demonstrated that the lethal dose for 50% at 30 days (LD50/30) of B6D2F1/J mice was 9.42 Gy. Antimicrobial therapy increased survival in radiation-injured (RI) mice. Combination therapy increased survival after RI and extended survival time but did not increase survival after CI. Sepsis began five days earlier in CI mice than RI mice with Gram-negative species predominating early and Gram-positive species increasing later. LVX plus AMX eliminated sepsis in CI and RI mice. STDCM-MPL eliminated Gram-positive bacteria in CI and most RI mice but not Gram-negative. Treatments significantly modulated 12 cytokines tested, which pertain to wound healing or elimination of infection. Conclusions: Combination therapy eliminates infection and prolongs survival time but does not assure CI mouse survival, suggesting that additional treatment for proliferative-cell recovery is required. PMID:25994812

Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice.

PubMed

Elliott, Thomas B; Bolduc, David L; Ledney, G David; Kiang, Juliann G; Fatanmi, Oluseyi O; Wise, Stephen Y; Romaine, Patricia L P; Newman, Victoria L; Singh, Vijay K

2015-01-01

A combination therapy for combined injury (CI) using a non-specific immunomodulator, synthetic trehalose dicorynomycolate and monophosphoryl lipid A (STDCM-MPL), was evaluated to augment oral antimicrobial agents, levofloxacin (LVX) and amoxicillin (AMX), to eliminate endogenous sepsis and modulate cytokine production. Female B6D2F(1)/J mice received 9.75 Gy cobalt-60 gamma-radiation and wound. Bacteria were isolated and identified in three tissues. Incidence of bacteria and cytokines were compared between treatment groups. Results demonstrated that the lethal dose for 50% at 30 days (LD(50/30)) of B6D2F(1)/J mice was 9.42 Gy. Antimicrobial therapy increased survival in radiation-injured (RI) mice. Combination therapy increased survival after RI and extended survival time but did not increase survival after CI. Sepsis began five days earlier in CI mice than RI mice with Gram-negative species predominating early and Gram-positive species increasing later. LVX plus AMX eliminated sepsis in CI and RI mice. STDCM-MPL eliminated Gram-positive bacteria in CI and most RI mice but not Gram-negative. Treatments significantly modulated 12 cytokines tested, which pertain to wound healing or elimination of infection. Combination therapy eliminates infection and prolongs survival time but does not assure CI mouse survival, suggesting that additional treatment for proliferative-cell recovery is required.

Clinical relevance of molecular identification of microorganisms and detection of antimicrobial resistance genes in bloodstream infections of paediatric cancer patients.

PubMed

Carlesse, Fabianne; Cappellano, Paola; Quiles, Milene Gonçalves; Menezes, Liana Carballo; Petrilli, Antonio Sérgio; Pignatari, Antonio Carlos

2016-09-01

Bloodstream infections (BSIs) are the major cause of mortality in cancer patients. Molecular techniques are used for rapid diagnosis of BSI, allowing early therapy and improving survival. We aimed to establish whether real-time quantitative polymerase chain reaction (qPCR) could improve early diagnosis and therapy in paediatric cancer patients, and describe the predominant pathogens of BSI and their antimicrobial susceptibility. Blood samples were processed by the BACTEC system and microbial identification and susceptibility tests were performed by the Phoenix system. All samples were screened by multiplex 16 s rDNA qPCR. Seventeen species were evaluated using sex-specific TaqMan probes and resistance genes blaSHV, blaTEM, blaCTX, blaKPC, blaIMP, blaSPM, blaVIM, vanA, vanB and mecA were screened by SYBR Green reactions. Therapeutic efficacy was evaluated at the time of positive blood culture and at final phenotypic identification and antimicrobial susceptibility results. We analyzed 69 episodes of BSI from 64 patients. Gram-positive bacteria were identified in 61 % of the samples, Gram-negative bacteria in 32 % and fungi in 7 %. There was 78.2 % of agreement between the phenotypic and molecular methods in final species identification. The mecA gene was detected in 81.4 % of Staphylococcus spp., and 91.6 % were concordant with the phenotypic method. Detection of vanA gene was 100 % concordant. The concordance for Gram-negative susceptibilities was 71.4 % for Enterobacteriaceae and 50 % for Pseudomonas aeruginosa. Therapy was more frequently inadequate in patients who died, and the molecular test was concordant with the phenotypic susceptibility test in 50 %. qPCR has potential indication for early identification of pathogens and antimicrobial resistance genes from BSI in paediatric cancer patients and may improve antimicrobial therapy.

Topical antimicrobial agents for the treatment of chronic wounds.

PubMed

Ousey, Karen; McIntosh, Caroline

2009-09-01

Chronic wounds are commonly observed in acute and community settings. The management of chronic wounds represents a significant proportion of health-care resources and makes up a substantial amount of contact time with community-based nurses spending approximately 25% to 50% of their time treating wounds. Chronic wounds often exhibit increased bacterial burden that can negatively impact upon patients, reduce their quality of life and substantially increase treatment costs for health care providers. Antibiotic resistance has become a major medical and public health problem, and interest has been generated in the use of topical therapies to manage wound infection. This article presents an overview of the historical use of honey, silver and iodine for the treatment of infected wounds progressing through to modern day use and the current evidence base for the use of these antimicrobial agents in the management of infected wounds.

Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy

PubMed Central

Nau, Gerard J.; Ross, Ted M.; Evans, Thomas G.; Chakraborty, Krishnendu; Empey, Kerry M.; Flynn, JoAnne L.

2014-01-01

Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The “Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy” session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials. PMID:25148426

Shigella species epidemiology and antimicrobial susceptibility: the implications of emerging azithromycin resistance for guiding treatment, guidelines and breakpoints.

PubMed

Brown, Jeremy D; Willcox, Simon J; Franklin, Neil; Hazelton, Briony; Howard, Peter; Reinten, Tracie; Sheppeard, Vicky; O'Sullivan, Matthew

2017-11-01

To examine antimicrobial susceptibility patterns and predictors of resistance among Shigella isolates in New South Wales (NSW), Australia during 2013-14 with emphasis on azithromycin. Cross-sectional analysis of all shigellosis cases (160) notified to public health authorities in NSW, Australia was performed. Among 160 Shigella isolates tested, 139 (86.9%) were susceptible to azithromycin, 104 (65.0%) to ciprofloxacin and 38 (23.7%) to co-trimoxazole. Ciprofloxacin resistance was 1.9 times more common in infections acquired in Australia compared with those acquired overseas, while azithromycin resistance was 8.5 times more common in males. We recommend ongoing reconsideration of guidelines for the treatment of shigellosis based on emerging resistance patterns. First-line therapy may need to be reconsidered based on local resistance rates due to common resistance to co-trimoxazole and ciprofloxacin. We recommend culture and susceptibility testing for suspected and proven shigellosis. Azithromycin susceptibility breakpoints for Shigella species may need to be species specific. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis.

PubMed

Georgopoulou, Antonia-Panagiota; Savva, Athina; Giamarellos-Bourboulis, Evangelos J; Georgitsi, Marianna; Raftogiannis, Maria; Antonakos, Nicolaos; Apostolidou, Efterpi; Carrer, Dionyssia-Pinelopi; Dimopoulos, George; Economou, Aggelos; Efthymiou, George; Galanakis, Nearchos; Galani, Labrini; Gargalianos, Panagiotis; Karaiskos, Ilias; Katsenos, Chrisostomos; Kavatha, Dimitra; Koratzanis, Evangelos; Labropoulos, Panagiotis; Lada, Malvina; Nakos, George; Paggalou, Evgenia; Panoutsopoulos, George; Paraschos, Michael; Pavleas, Ioannis; Pontikis, Konstantinos; Poulakou, Garyfallia; Prekates, Athanassios; Sybardi, Styliani; Theodorakopoulou, Maria; Trakatelli, Christina; Tsiaoussis, Panagiotis; Gogos, Charalambos; Giamarellou, Helen; Armaganidis, Apostolos; Meisner, Michael

2011-06-01

The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials. Copyright © 2011 Elsevier Inc. All rights reserved.

Photodynamic therapy for infections: clinical applications.

PubMed

Kharkwal, Gitika B; Sharma, Sulbha K; Huang, Ying-Ying; Dai, Tianhong; Hamblin, Michael R

2011-09-01

Photodynamic therapy (PDT) was discovered over 100 years ago by its ability to kill various microorganisms when the appropriate dye and light were combined in the presence of oxygen. However it is only in relatively recent times that PDT has been studied as a treatment for various types of localized infections. This resurgence of interest has been partly motivated by the alarming increase in drug resistance amongst bacteria and other pathogens. This review will focus on the clinical applications of antimicrobial PDT. The published peer-reviewed literature was reviewed between 1960 and 2011. The basics of antimicrobial PDT are discussed. Clinical applications of antimicrobial PDT to localized viral infections caused by herpes and papilloma viruses, and nonviral dermatological infections such as acne and other yeast, fungal and bacterial skin infections are covered. PDT has been used to treat bacterial infections in brain abscesses and non-healing ulcers. PDT for dental infections including periodontitis and endodontics has been well studied. PDT has also been used for cutaneous Leishmaniasis. Clinical trials of PDT and blue light alone therapy for gastric Helicobacter pylori infection are also covered. As yet clinical PDT for infections has been mainly in the field of dermatology using 5-aminolevulanic acid and in dentistry using phenothiazinium dyes. We expect more to see applications of PDT to more challenging infections using advanced antimicrobial photosensitizers targeted to microbial cells in the years to come. Copyright © 2011 Wiley-Liss, Inc.

Periodontal therapy using local delivery of antimicrobial agents.

PubMed

Niederman, Richard; Abdelshehid, George; Goodson, J Max

2002-10-01

Antimicrobial agents, systemic and/or local, are thought by some to be effective agents for treating periodontal infections. Here the authors determine the costs and benefits of local delivery agents for treating periodontal disease. Applying this cost-benefit analysis to patient care, however, will depend upon a clinician's expertise and a patient's value system.

Challenges for a Sustainable Financial Foundation for Antimicrobial Stewardship.

PubMed

Dik, Jan-Willem H; Sinha, Bhanu

2017-03-30

Antimicrobial resistance is a worldwide threat and a problem with large clinical and economic impact. Antimicrobial Stewardship Programs are a solution to curb resistance development. A problem of resistance is a separation of actions and consequences, financial and clinical. Such a separation makes it difficult to create support among stakeholders leading to a lack of sense of responsibility. To counteract the resistance development it is important to perform diagnostics and know how to interpret the results. One should see diagnostics, therapy and resistance as one single process. Within this process all involved stakeholders need to work together on a more institutional level. We suggest therefore a solution: combining diagnostics and therapy into one single financial product . Such a product should act as an incentive to perform correct diagnostics. It also makes it easier to cover the costs of an antimicrobial stewardship program, which is often overlooked. Finally, such a product involves all stakeholders in the process and does not lay the costs at one stakeholder and the benefits somewhere else, solving the misbalance that is present nowadays.

In vivo evolution of antimicrobial resistance in a series of Staphylococcus aureus patient isolates: the entire picture or a cautionary tale?

PubMed Central

van Hal, Sebastiaan J.; Steen, Jason A.; Espedido, Björn A.; Grimmond, Sean M.; Cooper, Matthew A.; Holden, Matthew T. G.; Bentley, Stephen D.; Gosbell, Iain B.; Jensen, Slade O.

2014-01-01

Objectives To obtain an expanded understanding of antibiotic resistance evolution in vivo, particularly in the context of vancomycin exposure. Methods The whole genomes of six consecutive methicillin-resistant Staphylococcus aureus blood culture isolates (ST239-MRSA-III) from a single patient exposed to various antimicrobials (over a 77 day period) were sequenced and analysed. Results Variant analysis revealed the existence of non-susceptible sub-populations derived from a common susceptible ancestor, with the predominant circulating clone(s) selected for by type and duration of antimicrobial exposure. Conclusions This study highlights the dynamic nature of bacterial evolution and that non-susceptible sub-populations can emerge from clouds of variation upon antimicrobial exposure. Diagnostically, this has direct implications for sample selection when using whole-genome sequencing as a tool to guide clinical therapy. In the context of bacteraemia, deep sequencing of bacterial DNA directly from patient blood samples would avoid culture ‘bias’ and identify mutations associated with circulating non-susceptible sub-populations, some of which may confer cross-resistance to alternate therapies. PMID:24047554

In vivo evolution of antimicrobial resistance in a series of Staphylococcus aureus patient isolates: the entire picture or a cautionary tale?

PubMed

van Hal, Sebastiaan J; Steen, Jason A; Espedido, Björn A; Grimmond, Sean M; Cooper, Matthew A; Holden, Matthew T G; Bentley, Stephen D; Gosbell, Iain B; Jensen, Slade O

2014-02-01

To obtain an expanded understanding of antibiotic resistance evolution in vivo, particularly in the context of vancomycin exposure. The whole genomes of six consecutive methicillin-resistant Staphylococcus aureus blood culture isolates (ST239-MRSA-III) from a single patient exposed to various antimicrobials (over a 77 day period) were sequenced and analysed. Variant analysis revealed the existence of non-susceptible sub-populations derived from a common susceptible ancestor, with the predominant circulating clone(s) selected for by type and duration of antimicrobial exposure. This study highlights the dynamic nature of bacterial evolution and that non-susceptible sub-populations can emerge from clouds of variation upon antimicrobial exposure. Diagnostically, this has direct implications for sample selection when using whole-genome sequencing as a tool to guide clinical therapy. In the context of bacteraemia, deep sequencing of bacterial DNA directly from patient blood samples would avoid culture 'bias' and identify mutations associated with circulating non-susceptible sub-populations, some of which may confer cross-resistance to alternate therapies.

Chitosan and cloxacillin combination improve antibiotic efficacy against different lifestyle of coagulase-negative Staphylococcus isolates from chronic bovine mastitis.

PubMed

Breser, María L; Felipe, Verónica; Bohl, Luciana P; Orellano, María S; Isaac, Paula; Conesa, Agustín; Rivero, Virginia E; Correa, Silvia G; Bianco, Ismael D; Porporatto, Carina

2018-03-23

Bovine mastitis affects the health of dairy cows and the profitability of herds worldwide. Coagulase-negative staphylococci (CNS) are the most frequently isolated pathogens in bovine intramammary infection. Based on the wide range of antimicrobial, mucoadhesive and immunostimulant properties demonstrated by chitosan, we have evaluated therapy efficiency of chitosan incorporation to cloxacillin antibiotic as well as its effect against different bacterial lifestyles of seven CNS isolates from chronic intramammary infections. The therapeutic effects of combinations were evaluated on planktonic cultures, bacterial biofilms and intracellular growth in mammary epithelial cells. We found that biofilms and intracellular growth forms offered a strong protection against antibiotic therapy. On the other hand, we found that chitosan addition to cloxacillin efficiently reduced the antibiotic concentration necessary for bacterial killing in different lifestyle. Remarkably, the combined treatment was not only able to inhibit bacterial biofilm establishment and increase preformed biofilm eradication, but it also reduced intracellular bacterial viability while it increased IL-6 secretion by infected epithelial cells. These findings provide a new approach to prophylactic drying therapy that could help to improve conventional antimicrobial treatment against different forms of bacterial growth in an efficient, safer and greener manner reducing multiresistant bacteria generation and spread.

Clinical significance of the infection-free interval in the management of acute bacterial exacerbations of chronic bronchitis.

PubMed

Chodosh, Sanford

2005-06-01

Rational and appropriate antibiotic use for patients with acute exacerbation of chronic bronchitis (AECB) is a major concern, as approximately half of these patients do not have a bacterial infection. Typically, the result of antimicrobial therapy for patients with acute bacterial exacerbation of chronic bronchitis (ABECB) is not eradication of the pathogen but resolution of the acute symptoms. However, the length of time before the next bacterial exacerbation can be another important variable, as the frequency of exacerbations will affect the overall health of the patient and the rate of lung deterioration over time. Clinical trials comparing antimicrobial therapies commonly measure resolution of symptoms in AECB patients as the primary end point, regardless of whether the exacerbation is documented as bacterial in nature. Ideally, the scientific approach to assessing the efficacy of antibiotic therapy for ABECB should include a measurement of acute bacterial eradication rates in patients with documented bronchial bacterial infection followed by measurement of the infection-free interval (IFI), ie, the time to the next ABECB. The use of these variables can provide a standard for comparing various antimicrobial therapies. As we learn more about how antibiotics can affect the IFI, treatment decisions should be adapted to ensure optimal management of ABECB for the long-term.

Nafcillin Enhances Innate Immune-Mediated Killing of Methicillin-Resistant Staphylococcus aureus

PubMed Central

Sakoulas, George; Okumura, Cheryl Y.; Thienphrapa, Wdee; Olson, Joshua; Nonejuie, Poochit; Dam, Quang; Dhand, Abhay; Pogliano, Joseph; Yeaman, Michael R.; Hensler, Mary E.; Bayer, Arnold S.; Nizet, Victor

2014-01-01

Based on in vitro synergy studies, the addition of nafcillin to daptomycin was used to treat refractory methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Daptomycin is a de facto cationic antimicrobial peptide in vivo, with antistaphylococcal mechanisms reminiscent of innate host defense peptides (HDPs). In this study, the effects of nafcillin on HDP activity against MRSA were examined in vitro and in vivo. Exposures to β-lactam antimicrobials in general, and nafcillin in particular, significantly increased killing of S. aureus by selected HDPs from, keratinocytes, neutrophils and platelets. This finding correlated with enhanced killing of MRSA by whole blood, neutrophils and keratinocytes after growth in nafcillin. Finally, nafcillin pretreatment ex vivo reduced MRSA virulence in a murine subcutaneous infection model. Despite the lack of direct activity against MRSA, these studies show potent, consistent, and generalized nafcillin-mediated ‘sensitization’ to increased killing of MRSA by various components of the innate host response. The use of nafcillin as adjunctive therapy in MRSA bacteremia merits further study and should be considered in cases refractory to standard therapy. PMID:24297496

An Assessment of an Outpatient Antimicrobial Therapy Program in a Rural Medical Center : A Retrospective Chart Review.

PubMed

Burkett, Matthew Shawn; Macci Bires, Angela; Cline, Thomas W; Knight, Anthony

Current literature supports outpatient parenteral antimicrobial therapy (OPAT). This article presents results from a research study that evaluated an OPAT program that treated community-acquired pneumonia. If patients had the opportunity to receive outpatient intravenous antibiotics for community-acquired pneumonia, would this prevent future hospitalization? Was there a decrease in hospital admissions? An informal cost-benefit analysis comparing OPAT with inpatient hospital admissions for the same disease was also reviewed to provide evidence whether there was a change. What was the overall health care cost savings? The medical charts of 50 patients with confirmed pneumonia who had received OPAT in a 3-month period were reviewed. A retrospective medical record review was performed. All patients were evaluated by the in-house OPAT team. The resulting analysis provided evidence that an estimated savings of approximately $2100 per day would be achieved by decreasing hospital readmissions for patient who had been treated with OPAT. The conclusion of this study provides evidence that the implement of an OPAT program was, and is, essential for patient care and evidence-based best practice adherence.

[CHRONIC PERIODONTITIS WITH SYMPTOMATIC HYPERTROPHIC GINGIVITIS: CASE REPORT AND REVIEW OF THE LITERATURE].

PubMed

Shinkevich, V; Udaltsova, K; Pisarenko, E; Kolomiets, S; Khmil, T

2015-12-01

Gingivitis in traditional national dentistry referred to independent diseases or symptomatic condition in periodontitis and classified morphologically. The diagnostic features of the diseases are characteristic, but the clinical presentation of symptomatic gingivitis and patterns of bone destructions may vary between patients. Successful treatment of the disease depends from proper diagnosis and advanced disease stages, but for symptomatic gingivitis that accompanying chronic periodontitis, protocols include surgical excision. Despite of the high prevalence of chronic generalized periodontitis, its active treatment often start in severe destruction and bone loss (2-3 stage severity). Today etiotropic antimicrobial therapy is real way to control microbial biofilm and has solid evidence base. Applying of etiotropic antimicrobial therapy as systemic azithromycin with timely treatment of mild to moderate periodontal and bone destruction may reduce severe periodontitis incidence of and treatment-related complications in the future. This paper attempts to describe the clinical diagnostic features and the current treatment options along with a suggested protocol for comprehensive management of chronic generalized periodontitis and hypertrophic gingivitis patient with case reports and a brief review.

Trends in antimicrobial resistance and empiric antibiotic therapy of bloodstream infections at a general hospital in Mid-Norway: a prospective observational study.

PubMed

Mehl, Arne; Åsvold, Bjørn Olav; Kümmel, Angela; Lydersen, Stian; Paulsen, Julie; Haugan, Ingvild; Solligård, Erik; Damås, Jan Kristian; Harthug, Stig; Edna, Tom-Harald

2017-02-02

The occurrence of bloodstream infection (BSI) and antimicrobial resistance have been increasing in many countries. We studied trends in antimicrobial resistance and empiric antibiotic therapy at a medium-sized general hospital in Mid-Norway. Between 2002 and 2013, 1995 prospectively recorded episodes of BSI in 1719 patients aged 16-99 years were included. We analyzed the antimicrobial non-susceptibility according to place of acquisition, site of infection, microbe group, and time period. There were 934 community-acquired (CA), 787 health care-associated (HCA) and 274 hospital-acquired (HA) BSIs. The urinary tract was the most common site of infection. Escherichia coli was the most frequently isolated infective agent in all three places of acquisition. Second in frequency was Streptococcus pneumoniae in CA and Staphylococcus aureus in both HCA and HA. Of the BSI microbes, 3.5% were non-susceptible to the antimicrobial regimen recommended by the National Professional Guidelines for Use of Antibiotics in Hospitals, consisting of penicillin, gentamicin, and metronidazole (PGM). In contrast, 17.8% of the BSI microbes were non-susceptible to cefotaxime and 27.8% were non-susceptible to ceftazidime. Antimicrobial non-susceptibility differed by place of acquisition. For the PGM regimen, the proportions of non-susceptibility were 1.4% in CA, 4.8% in HCA, and 6.9% in HA-BSI (p < 0.001), and increasing proportions of non-susceptibility over time were observed in HA-BSI, 2.2% in 2002-2005, 6.2% in 2006-2009, and 11.7% in 2010-2013 (p = 0.026), mainly caused by inherently resistant microbes. We also observed increasing numbers of bacteria with acquired resistance, particularly E. coli producing ESBL or possessing gentamicin resistance, and these occurred predominantly in CA- and HCA-BSI. Generally, antimicrobial resistance was a far smaller problem in our BSI cohort than is reported from countries outside Scandinavia. In our cohort, appropriate empiric antibiotic therapy could be achieved to a larger extent by replacing second- and third-generation cephalosporins with penicillin-gentamicin or piperacillin-tazobactam.

Antimicrobial consumption on Austrian dairy farms: an observational study of udder disease treatments based on veterinary medication records

PubMed Central

Käsbohrer, Annemarie; Schleicher, Corina; Fuchs, Klemens; Egger-Danner, Christa; Mayerhofer, Martin; Schobesberger, Hermann; Köfer, Josef; Obritzhauser, Walter

2017-01-01

Background Antimicrobial use in livestock production is an important contemporary issue, which is of public interest worldwide. Antimicrobials are not freely available to Austrian farmers and can only be administered to livestock by veterinarians, or by farmers who are trained members of the Animal Health Service. Since 2015, veterinarians have been required by law to report antimicrobials dispensed to farmers for use in food-producing animals. The study presented here went further than the statutory framework, and collected data on antimicrobials dispensed to farmers and those administered by veterinarians. Methods Seventeen veterinary practices were enrolled in the study via convenience sampling. These veterinarians were asked to contact interested dairy farmers regarding participation in the study (respondent-driven sampling). Data were collected from veterinary practice software between 1st October 2015 and 30th September 2016. Electronic data (89.4%) were transferred via an online interface and paper records (10.6%) were entered by the authors. Antimicrobial treatments with respect to udder disease were analysed by number of defined daily doses per cow and year (nDDDvet/cow/year), based on the European Medicines Agency technical unit, Defined Daily Dose for animals (DDDvet). Descriptive statistics and the Wilcoxon rank sum test were used to analyse the results. Results Antimicrobial use data from a total of 248 dairy farms were collected during the study, 232 of these farms treated cows with antibiotics; dry cow therapy was excluded from the current analysis. The mean number of DDDvet/cow/year for the antimicrobial treatment of all udder disease was 1.33 DDDvet/cow/year. Of these treatments, 0.73 DDDvet/cow/year were classed as highest priority critically important antimicrobials (HPCIAs), according to the World Health Organization (WHO) definition. The Wilcoxon rank sum test determined a statistically significant difference between the median number of DDDvet/cow/year for acute and chronic mastitis treatment (W = 10,734, p < 0.001). The most commonly administered antimicrobial class for the treatment of acute mastitis was beta-lactams. Intramammary penicillin was used at a mean of 0.63 DDDvet/cow/year, followed by the third generation cephalosporin, cefoperazone, (a HPCIA) at 0.60 DDDvet/cow/year. Systemic antimicrobial treatments were used at a lower overall level than intramammary treatments for acute mastitis. Discussion This study demonstrated that Austrian dairy cows in the study population were treated with antimicrobial substances for udder diseases at a relatively low frequency, however, a substantial proportion of these treatments were with substances considered critically important for human health. While it is vital that sick cows are treated, reductions in the overall use of antimicrobials, and critically important substances in particular, are still possible. PMID:29158993

Antimicrobial consumption on Austrian dairy farms: an observational study of udder disease treatments based on veterinary medication records.

PubMed

Firth, Clair L; Käsbohrer, Annemarie; Schleicher, Corina; Fuchs, Klemens; Egger-Danner, Christa; Mayerhofer, Martin; Schobesberger, Hermann; Köfer, Josef; Obritzhauser, Walter

2017-01-01

Antimicrobial use in livestock production is an important contemporary issue, which is of public interest worldwide. Antimicrobials are not freely available to Austrian farmers and can only be administered to livestock by veterinarians, or by farmers who are trained members of the Animal Health Service. Since 2015, veterinarians have been required by law to report antimicrobials dispensed to farmers for use in food-producing animals. The study presented here went further than the statutory framework, and collected data on antimicrobials dispensed to farmers and those administered by veterinarians. Seventeen veterinary practices were enrolled in the study via convenience sampling. These veterinarians were asked to contact interested dairy farmers regarding participation in the study (respondent-driven sampling). Data were collected from veterinary practice software between 1st October 2015 and 30th September 2016. Electronic data (89.4%) were transferred via an online interface and paper records (10.6%) were entered by the authors. Antimicrobial treatments with respect to udder disease were analysed by number of defined daily doses per cow and year (nDDD vet /cow/year), based on the European Medicines Agency technical unit, Defined Daily Dose for animals (DDD vet ). Descriptive statistics and the Wilcoxon rank sum test were used to analyse the results. Antimicrobial use data from a total of 248 dairy farms were collected during the study, 232 of these farms treated cows with antibiotics; dry cow therapy was excluded from the current analysis. The mean number of DDD vet /cow/year for the antimicrobial treatment of all udder disease was 1.33 DDD vet /cow/year. Of these treatments, 0.73 DDD vet /cow/year were classed as highest priority critically important antimicrobials (HPCIAs), according to the World Health Organization (WHO) definition. The Wilcoxon rank sum test determined a statistically significant difference between the median number of DDD vet /cow/year for acute and chronic mastitis treatment ( W  = 10,734, p  < 0.001). The most commonly administered antimicrobial class for the treatment of acute mastitis was beta-lactams. Intramammary penicillin was used at a mean of 0.63 DDD vet /cow/year, followed by the third generation cephalosporin, cefoperazone, (a HPCIA) at 0.60 DDD vet /cow/year. Systemic antimicrobial treatments were used at a lower overall level than intramammary treatments for acute mastitis. This study demonstrated that Austrian dairy cows in the study population were treated with antimicrobial substances for udder diseases at a relatively low frequency, however, a substantial proportion of these treatments were with substances considered critically important for human health. While it is vital that sick cows are treated, reductions in the overall use of antimicrobials, and critically important substances in particular, are still possible.

Antimicrobial consumption, costs and resistance patterns: a two year prospective study in a Romanian intensive care unit.

PubMed

Axente, Carmen; Licker, Monica; Moldovan, Roxana; Hogea, Elena; Muntean, Delia; Horhat, Florin; Bedreag, Ovidiu; Sandesc, Dorel; Papurica, Marius; Dugaesescu, Dorina; Voicu, Mirela; Baditoiu, Luminita

2017-05-22

Due to the vulnerable nature of its patients, the wide use of invasive devices and broad-spectrum antimicrobials used, the intensive care unit (ICU) is often called the epicentre of infections. In the present study, we quantified the burden of hospital acquired pathology in a Romanian university hospital ICU, represented by antimicrobial agents consumption, costs and local resistance patterns, in order to identify multimodal interventional strategies. Between 1 st January 2012 and 31 st December 2013, a prospective study was conducted in the largest ICU of Western Romania. The study group was divided into four sub-samples: patients who only received prophylactic antibiotherapy, those with community-acquired infections, patients who developed hospital acquired infections and patients with community acquired infections complicated by hospital-acquired infections. The statistical analysis was performed using the EpiInfo version 3.5.4 and SPSS version 20. A total of 1596 subjects were enrolled in the study and the recorded consumption of antimicrobial agents was 1172.40 DDD/ 1000 patient-days. The presence of hospital acquired infections doubled the length of stay (6.70 days for patients with community-acquired infections versus 16.06/14.08 days for those with hospital-acquired infections), the number of antimicrobial treatment days (5.47 in sub-sample II versus 11.18/12.13 in sub-samples III/IV) and they increased by 4 times compared to uninfected patients. The perioperative prophylactic antibiotic treatment had an average length duration of 2.78 while the empirical antimicrobial therapy was 3.96 days in sample II and 4.75/4.85 days for the patients with hospital-acquired infections. The incidence density of resistant strains was 8.27/1000 patient-days for methicilin resistant Staphylococcus aureus, 7.88 for extended spectrum β-lactamase producing Klebsiella pneumoniae and 4.68/1000 patient-days for multidrug resistant Acinetobacter baumannii. Some of the most important circumstances collectively contributing to increasing the consumption of antimicrobials and high incidence densities of multidrug-resistant bacteria in the studied ICU, are represented by prolonged chemoprophylaxis and empirical treatment and also by not applying the definitive antimicrobial therapy, especially in patients with favourable evolution under empirical antibiotic treatment. The present data should represent convincing evidence for policy changes in the antibiotic therapy.

Low-cost periodontal therapy.

PubMed

Slots, Jørgen

2012-10-01

Periodontitis is a complex infectious disease that affects low-income individuals disproportionately. Periodontitis is associated with specific bacterial species and herpesviruses, and successful prevention and treatment of the disease is contingent upon effective control of these pathogens. This article presents an efficacious, highly safe, minimally invasive, practical and low-cost periodontal therapy that involves professional and patient-administered mechanical therapy and antimicrobial agents. The major components are scaling for calculus removal, periodontal pocket irrigation with potent antiseptics, and treatment with systemic antibiotics for advanced disease. Povidone-iodine and sodium hypochlorite have all the characteristics for becoming the first-choice antiseptics in the management of periodontal diseases. Both agents show excellent antibacterial and antiviral properties, are readily available throughout the world, have been safely used in periodontal therapy for decades, offer significant benefits for individuals with very limited financial resources, and are well accepted by most dental professionals and patients. Four per cent chlorhexidine applied with a toothbrush to the most posterior part to the tongue dorsum can markedly reduce or eliminate halitosis in most individuals. Systemic antibiotics are used to treat periodontopathic bacteria that are not readily reached by topical therapy, such as pathogens within gingival tissue, within furcation defects, at the base of periodontal pockets, and on the tongue, tonsils and buccal mucosae. Valuable antibiotic therapies are amoxicillin-metronidazole (250 mg of amoxicillin and 250 mg of metronidazole, three times daily for 8 days) for young and middle-aged patients, and ciprofloxacin-metronidazole (500 mg of each, twice daily for 8 days) for elderly patients and for patients in developing countries who frequently harbor enteric rods subgingivally. Scaling to remove dental calculus and the prudent use of inexpensive antimicrobial agents can significantly retard or arrest progressive periodontitis in the great majority of patients. © 2012 John Wiley & Sons A/S.

Point-of-care Beta-lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation.

PubMed

Leis, Jerome A; Palmay, Lesley; Ho, Grace; Raybardhan, Sumit; Gill, Suzanne; Kan, Tiffany; Campbell, Jackie; Kiss, Alex; McCready, Janine B; Das, Pavani; Minnema, Brian; Powis, Jeff E; Walker, Sandra A N; Ferguson, Heather; Wong, Benny; Weber, Elizabeth

2017-06-01

Beta-lactam allergy skin testing (BLAST) is recommended by antimicrobial stewardship program (ASP) guidelines, yet few studies have systematically evaluated its impact when delivered at point-of-care. We conducted a pragmatic multicenter prospective evaluation of the use of point-of-care BLAST by ASPs. In staggered 3-month intervals, ASP teams at three hospitals received training by allergists to offer BLAST for eligible patients with infectious diseases receiving non-preferred beta-lactam therapy due to severity of their allergy. The primary outcome was the proportion of patients receiving the preferred beta-lactam therapy. Of 827 patients with reported beta-lactam allergy over 15-months, beta-lactam therapy was preferred among 632(76%). During baseline periods, 50% (124/246) received preferred beta-lactam therapy based on history, compared with 60% (232/386) during the intervention periods (p=0.02), which improved further to 81% (313/386) upon provision of BLAST (p<0.001) without any increase in incidence of adverse drug reactions (4% vs. 3%; p=0.4). After adjusting for patient variables and the correlation between hospitals, the intervention period was associated with a 4.5-fold greater odds of receiving preferred beta-lactam therapy (95% CI, 2.4-8.2; p<0.0001). The use of BLAST at the point-of-care across three hospital ASPs resulted in greater use of preferred beta-lactam therapy without increasing the risk of adverse drug reactions. Longer term studies are needed to better assess the safety and clinical impact of this ASP intervention. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Preemptive Ethanol Lock Therapy in Pediatric Hematology/Oncology Patients With Catheter-Associated Bloodstream Infection: Impact on Length of Stay, Cost, and Catheter Salvage.

PubMed

McGrath, Eric; Du, Wei; Rajpurkar, Madhvi

2018-03-01

Ethanol lock therapy (ELT) with systemic antimicrobial therapy is a promising therapy for catheter-related infection (CRI). The impact of ELT timing on treatment efficacy and costs is unknown. A prospective study was conducted in the Hematology/Oncology Unit at the Children's Hospital of Michigan. Patients with suspected CRI were randomized to Preemptive ELT arm or Rescue ELT arm after positive culture. Five cases in Preemptive arm and 9 in Rescue arm had a confirmed CRI. All cases cleared infection with line salvage with no adverse events due to ELT or recurrence within 14 days. Our data showed a trend toward 36% reduction in average hospital costs and 40% reduction in average length of stay in Preemptive arm over Rescue arm. Although a small study, our data on preemptive ELT with systemic antimicrobial therapy suggest a potentially important treatment strategy in reducing length of stay as well as hospital costs.

Polymeric Nanoparticle-Based Photodynamic Therapy for Chronic Periodontitis in Vivo.

PubMed

de Freitas, Laura Marise; Calixto, Giovana Maria Fioramonti; Chorilli, Marlus; Giusti, Juçaíra Stella M; Bagnato, Vanderlei Salvador; Soukos, Nikolaos S; Amiji, Mansoor M; Fontana, Carla Raquel

2016-05-20

Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT-in planktonic and biofilm phases-with MB or MB-NP (25 µg/mL) at 20 J/cm² in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm²) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment.

Severe soft tissue infections.

PubMed

Napolitano, Lena M

2009-09-01

Severe skin and soft tissue infections (SSTIs) frequently require management in the ICU, in part related to associated septic shock or toxic shock syndrome or associated organ failure. Four fundamental management principles are key to a successful outcome in caring for patients who have severe SSTIs, including (1) early diagnosis and differentiation of necrotizing versus nonnecrotizing SSTI, (2) early initiation of appropriate empiric broad-spectrum antimicrobial therapy with consideration of risk factors for specific pathogens and mandatory coverage for methicillin-resistant Staphylococcus aureus (MRSA), (3) source control (ie, early aggressive surgical intervention for drainage of abscesses and debridement of necrotizing soft tissue infections), and (4) pathogen identification and appropriate de-escalation of antimicrobial therapy. MRSA has emerged as the most common identifiable cause of severe SSTIs; therefore, initiation of empiric anti-MRSA antimicrobials is warranted in all cases of severe SSTIs. In addition, appropriate critical care management-including fluid resuscitation, organ support and nutritional support-is a necessary component in treating severe SSTIs.

Herd-level relationship between antimicrobial use and presence or absence of antimicrobial resistance in gram-negative bovine mastitis pathogens on Canadian dairy farms.

PubMed

Saini, Vineet; McClure, J T; Scholl, Daniel T; DeVries, Trevor J; Barkema, Herman W

2013-08-01

Concurrent data on antimicrobial use (AMU) and resistance are needed to contain antimicrobial resistance (AMR) in bacteria. The present study examined a herd-level association between AMU and AMR in Escherichia coli (n=394) and Klebsiella species (n=139) isolated from bovine intramammary infections and mastitis cases on 89 dairy farms in 4 regions of Canada [Alberta, Ontario, Québec, and Maritime Provinces (Prince Edward Island, Nova Scotia, and New Brunswick)]. Antimicrobial use data were collected using inventory of empty antimicrobial containers and antimicrobial drug use rate was calculated to quantify herd-level AMU. Minimum inhibitory concentrations (MIC) were determined using Sensititre National Antimicrobial Resistance Monitoring System (NARMS) gram-negative MIC plate (Trek Diagnostic Systems Inc., Cleveland, OH). Isolates were classified as susceptible, intermediate, or resistant. Intermediate and resistant category isolates were combined to form an AMR category, and multivariable logistic regression models were built to determine herd-level odds of AMR to tetracycline, ampicillin, cefoxitin, chloramphenicol, trimethoprim-sulfamethoxazole combination, sulfisoxazole, streptomycin and kanamycin in E. coli isolates. In the case of Klebsiella species isolates, logistic regression models were built for tetracycline and sulfisoxazole; however, no associations between AMU and AMR in Klebsiella species were observed. Ampicillin-intermediate or -resistant E. coli isolates were associated with herds that used intramammarily administered cloxacillin, penicillin-novobiocin combination, and cephapirin used for dry cow therapy [odds ratios (OR)=26, 32, and 189, respectively], and intramammary ceftiofur administered for lactating cow therapy and systemically administered penicillin (OR=162 and 2.7, respectively). Use of systemically administered penicillin on a dairy farm was associated with tetracycline and streptomycin-intermediate or -resistant E. coli isolates (OR=5.6 and 2.8, respectively). Use of cephapirin and cloxacillin administered intramammarily for dry cow therapy was associated with increasing odds of having at least 1 kanamycin-intermediate or -resistant E. coli isolate at a farm (OR=8.7 and 9.3, respectively). Use of systemically administered tetracycline and ceftiofur was associated with cefoxitin-intermediate or -resistant E. coli (OR=0.13 and 0.16, respectively); however, the odds of a dairy herd having at least 1 cefoxitin-intermediate or -resistant E. coli isolate due to systemically administered ceftiofur increased with increasing average herd parity (OR=3.1). Association between herd-level AMU and AMR in bovine mastitis coliforms was observed for certain antimicrobials. Differences in AMR between different barn types and geographical regions were not observed. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Outpatient management of febrile neutropenia associated with cancer chemotherapy: risk stratification and treatment review.

PubMed

Pherwani, Nisha; Ghayad, Joanna M; Holle, Lisa M; Karpiuk, Emilie L

2015-04-15

Strategies for the management of chemotherapy-induced febrile neutropenia (FN), including assessment tools for determining which patients are at low risk for FN complications and can be treated in the outpatient setting, are discussed. Due to the potential for life-threatening complications, the development of FN in patients receiving cancer chemotherapy traditionally prompted hospitalization and i.v. antimicrobial therapy, but there is convincing published evidence that an identifiable subset of patients can be safely treated as outpatients. Two validated assessment tools recommended for identifying patients at low risk for FN complications are the Talcott classification system and the Multinational Association for Supportive Care in Cancer (MASCC) risk index; the MASCC index is superior in terms of sensitivity and negative predictive value but has lower specificity. In low-risk FN cases, outpatient oral antimicrobial therapy has been shown to be a safe and effective alternative to i.v. therapy for both inpatients and outpatients; current practice guidelines recommend an oral fluoroquinolone (e.g., ciprofloxacin) in combination with oral amoxicillin-clavulanate. The guidelines emphasize that in certain cases of FN (e.g., those involving prolonged or pronounced neutropenia or serious comorbidities), inpatient i.v. therapy is required. Pharmacists can play an important role in the management of chemotherapy-associated FN through involvement in risk assessment to identify candidates for outpatient oral antimicrobial therapy, selection of appropriate pharmacotherapy, drug therapy monitoring, and development of institutional guidelines or pathways. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Occurrence of ß-lactamase genes among non-Typhi Salmonella enterica isolated from humans, food animals, and retail meats in the United States and Canada

USDA-ARS?s Scientific Manuscript database

Non-Typhi Salmonella cause over 1.7 million cases of gastroenteritis in North America each year, and food-animal products are commonly implicated in human infections. For invasive infections, antimicrobial therapy is implicated. In North America, the antimicrobial susceptibility of Salmonella is m...

[Undulant fever and autoimmune hemolytic anemia in a 20-year-old exchange student from Jordan - the human brucellosis as an important differential diagnosis in migrants].

PubMed

Trawinski, Henning; Gräber, Sandra; Leifels, Michael; Schubert, Stefan; Lübbert, Christoph

2015-12-01

A 20-year-old Jordanian exchange student presents with recurrent fever, night sweats, cough, and swelling and redness around the ankle. Physical examination further reveals bilateral ankle arthritis and painful cervical lymphadenopathy. Laboratory tests show signs of autoimmune hemolytic anemia, elevated liver function tests, and moderate laboratory signs of inflammation. All blood cultures reveal growth of gram-negative coccoid rods which are initially identified by mass spectrometry as Moraxella lacunata and Ochrobactrum anthropi. However, antimicrobial therapy with imipenem / cilastatin does not improve the patient's clinical condition. Based on the travel history including consumption of yogurt from unpasteurized sheep's milk, we perform serological tests with a strongly positive result for Brucella species, and additional work-up of blood culture isolates confirm the definitive diagnosis of brucellosis (Malta fever, infection by Brucella melitensis). After initiation of antimicrobial therapy with doxycycline and rifampin the patient shows complete resolution of fever. Arthritis, autoimmune hemolytic anemia and accompanying hepatitis improve in the course. Thus, since brucellosis is endemic to countries like Jordan, it should be considered as a possible agent of fever of unknown origin especially in migrants unresponsive to empiric therapy and appropriate diagnostic tests including meticulous validation of blood cultures should be performed. Standard therapy is a combination of doxycycline with rifampin for at least 6 weeks. © Georg Thieme Verlag KG Stuttgart · New York.

Risk factors for acquisition of OXA-48-producing Klebsiella pneumonia among contact patients: a multicentre study.

PubMed

Hilliquin, D; Le Guern, R; Thepot Seegers, V; Neulier, C; Lomont, A; Marie, V; Legeay, C; Merrer, J; Lepelletier, D; Rogues, A M; Grandbastien, B; Lucet, J C; Zahar, J R

2018-03-01

Cohorting carbapenemase-producing Enterobacteriaceae (CPE) carriers during hospitalization limits in-hospital spreading. To identify risk factors for CPE acquisition among contacts of an index patient in non-cohorted populations. A multicentre retrospective matched case-control study was conducted in five hospitals. Each contact patient (case) who acquired Klebsiella pneumoniae (KP)-OXA-48 from an index patient was compared to three contact (controls) with the same index patients matched with hospitalization in the same unit and similar exposure times. Fifty-one secondary cases and 131 controls were included. By univariate analysis, exposure time (odds ratio: 1.06; 95% confidence interval: 1.02-1.1; P = 0.006), concomitant infection at admission (3.23; 1.42-7.35; P = 0.005), antimicrobial therapy within the last month before hospitalization (2.88; 1.34-6.2; P = 0.007), antimicrobial therapy during the exposure time (5.36; 2.28-12.6; P < 0.001), use of at least one invasive procedure (2.99; 1.25-7.15; P = 0.014), number of invasive procedures (1.52; 1.05-2.19; P = 0.025), and geographical proximity (2.84; 1.15-7.00; P = 0.023) were associated with CPE acquisition. By multivariate analysis, antimicrobial therapy during the exposure time (odds ratio: 6.36; 95% confidence interval: 2.46-16.44; P < 0.001), at least one invasive procedure (2.92; 1.04-8.17; P = 0.041), and geographical proximity (3.69; 1.15-11.86; P = 0.028) were associated with acquisition. In this study, geographical proximity, invasive procedure, and antimicrobial therapy during exposure time were significantly associated with KP-OXA-48 acquisition. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Marine Pseudomonas putida: a potential source of antimicrobial substances against antibiotic-resistant bacteria.

PubMed

Marinho, Palloma Rodrigues; Moreira, Ana Paula Barbosa; Pellegrino, Flávia Lúcia Piffano Costa; Muricy, Guilherme; Bastos, Maria do Carmo de Freire; Santos, Kátia Regina Netto dos; Giambiagi-deMarval, Marcia; Laport, Marinella Silva

2009-08-01

Bacteria isolated from marine sponges found off the coast of Rio de Janeiro, Brazil, were screened for the production of antimicrobial substances. We report a new Pseudomonas putida strain (designated P. putida Mm3) isolated from the sponge Mycale microsigmatosa that produces a powerful antimicrobial substance active against multidrug-resistant bacteria. P. putida Mm3 was identified on the basis of 16S rRNA gene sequencing and phenotypic tests. Molecular typing for Mm3 was performed by RAPD-PCR and comparison of the results to other Pseudomonas strains. Our results contribute to the search for new antimicrobial agents, an important strategy for developing alternative therapies to treat infections caused by multidrug-resistant bacteria.

Gonococcal endocarditis in a 47-year-old Japanese man.

PubMed

Ito, Hiroshi; Miyazaki, Shinichi; Ozeki, Takaya; Matsuo, Masaki; Branch, Joel; Fujita, Yoshiro; Marui, Nobuyuki

2014-01-01

A 47-year-old sexually active Japanese man was admitted with a persistent fever and weight loss. A physical examination revealed a cardiac murmur. A transthoracic echocardiogram was nondiagnostic, although blood cultures grew Neisseria gonorrhoeae. Gonococcal endocarditis was diagnosed based on the modified Duke criteria. The administration of antimicrobial therapy resulted in an adequate initial resolution; however, two months after completing the therapy, the patient developed cardiac failure. Severe aortic regurgitation was identified, and the patient underwent emergent aortic valve replacement. Despite the rarity of gonococcal endocarditis, this disease should nevertheless be considered in patients presenting with a fever, cardiac murmur and a consistent sexual history.

Cationic antimicrobial polymers and their assemblies.

PubMed

Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

2013-05-10

Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications.

Cationic Antimicrobial Polymers and Their Assemblies

PubMed Central

Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

2013-01-01

Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications. PMID:23665898

Trends in antibiotic use and microbial diagnostics in periodontal treatment: comparing surveys of German dentists in a ten-year period.

PubMed

Falkenstein, Svenja; Stein, Jamal M; Henne, Karsten; Conrads, Georg

2016-11-01

The use of antibiotics and microbial tests in periodontal treatment among German dental practitioners was investigated in 2012-2013 and compared with 2002-2003 data. One thousand four hundred representative German practitioners received a postal questionnaire requesting their prescribing habits concerning type, dose, frequency, and sequence of antibiotics adjunctive to mechanical debridement. Additionally, the use of local antimicrobials and microbial tests were recorded. The response rate was 29.1 % (407 reports). Drug combinations, especially amoxicillin plus metronidazole, were prescribed most frequently (32.8 %) with an increase of 7.4 % during the past decade, followed by clindamycin (29.3 %). Amoxicillin monotherapy was used unexpectedly frequently (17.0 %) and doxycycline (2.8 %) very infrequently. Then, 24.7 % prescribed antibiotics prior to mechanical therapy, while most dentists followed the recommended sequence. The use of local antimicrobials increased by 6.2 % and of microbial diagnostics by 20.8 %. Positive trends regarding position-paper-conform prescribing habits including the scheduling of systemic antibiotics and increasing use of local antimicrobials and microbial tests were observed. However, deficits and malpractice still exist in German practices. Unexpected is the widespread and increasing use of clindamycin. Continuing educational campaigns and strictly expressed real guidelines are needed. Indication and choice of antibiotic agents in causal periodontal therapy among German dentists have changed between 2003 and 2013 toward a more position-paper-based concept, but inappropriate prescriptions of second choice antibiotics still remain conspicuous.

Experience With Rapid Microarray-Based Diagnostic Technology and Antimicrobial Stewardship for Patients With Gram-Positive Bacteremia.

PubMed

Neuner, Elizabeth A; Pallotta, Andrea M; Lam, Simon W; Stowe, David; Gordon, Steven M; Procop, Gary W; Richter, Sandra S

2016-11-01

OBJECTIVE To describe the impact of rapid diagnostic microarray technology and antimicrobial stewardship for patients with Gram-positive blood cultures. DESIGN Retrospective pre-intervention/post-intervention study. SETTING A 1,200-bed academic medical center. PATIENTS Inpatients with blood cultures positive for Staphylococcus aureus, Enterococcus faecalis, E. faecium, Streptococcus pneumoniae, S. pyogenes, S. agalactiae, S. anginosus, Streptococcus spp., and Listeria monocytogenes during the 6 months before and after implementation of Verigene Gram-positive blood culture microarray (BC-GP) with an antimicrobial stewardship intervention. METHODS Before the intervention, no rapid diagnostic technology was used or antimicrobial stewardship intervention was undertaken, except for the use of peptide nucleic acid fluorescent in situ hybridization and MRSA agar to identify staphylococcal isolates. After the intervention, all Gram-positive blood cultures underwent BC-GP microarray and the antimicrobial stewardship intervention consisting of real-time notification and pharmacist review. RESULTS In total, 513 patients with bacteremia were included in this study: 280 patients with S. aureus, 150 patients with enterococci, 82 patients with stretococci, and 1 patient with L. monocytogenes. The number of antimicrobial switches was similar in the pre-BC-GP (52%; 155 of 300) and post-BC-GP (50%; 107 of 213) periods. The time to antimicrobial switch was significantly shorter in the post-BC-GP group than in the pre-BC-GP group: 48±41 hours versus 75±46 hours, respectively (P<.001). The most common antimicrobial switch was de-escalation and time to de-escalation, was significantly shorter in the post-BC-GP group than in the pre-BC-GP group: 53±41 hours versus 82±48 hours, respectively (P<.001). There was no difference in mortality or hospital length of stay as a result of the intervention. CONCLUSIONS The combination of a rapid microarray diagnostic test with an antimicrobial stewardship intervention improved time to antimicrobial switch, especially time to de-escalation to optimal therapy, in patients with Gram-positive blood cultures. Infect Control Hosp Epidemiol 2016;1-6.

Chronic Lyme disease: misconceptions and challenges for patient management

PubMed Central

Halperin, John J

2015-01-01

Lyme disease, infection with the tick-borne spirochete Borrelia burgdorferi, causes both specific and nonspecific symptoms. In untreated chronic infection, specific manifestations such as a relapsing large-joint oligoarthritis can persist for years, yet subside with appropriate antimicrobial therapy. Nervous system involvement occurs in 10%–15% of untreated patients and typically involves lymphocytic meningitis, cranial neuritis, and/or mononeuritis multiplex; in some rare cases, patients have parenchymal inflammation in the brain or spinal cord. Nervous system infection is similarly highly responsive to antimicrobial therapy, including oral doxycycline. Nonspecific symptoms such as fatigue, perceived cognitive slowing, headache, and others occur in patients with Lyme disease and are indistinguishable from comparable symptoms occurring in innumerable other inflammatory states. There is no evidence that these nonspecific symptoms reflect nervous system infection or damage, or that they are in any way specific to or diagnostic of this or other tick-borne infections. When these symptoms occur in patients with Lyme disease, they typically also subside after antimicrobial treatment, although this may take time. Chronic fatigue states have been reported to occur following any number of infections, including Lyme disease. The mechanism underlying this association is unclear, although there is no evidence in any of these infections that these chronic posttreatment symptoms are attributable to ongoing infection with B. burgdorferi or any other identified organism. Available appropriately controlled studies indicate that additional or prolonged courses of antimicrobial therapy do not benefit patients with a chronic fatigue-like state after appropriately treated Lyme disease. PMID:26028977

Systematic review of antimicrobial lock therapy for prevention of central-line-associated bloodstream infections in adult and pediatric cancer patients.

PubMed

Norris, LeAnn B; Kablaoui, Farah; Brilhart, Maggie K; Bookstaver, P Brandon

2017-09-01

Central venous catheter (CVC) use is commonplace in cancer patients. Antimicrobial lock therapy (ALT), the instillation of a concentrated antimicrobial solution into the catheter lumen, is one method for preventing infection among CVCs. This systematic review discusses the effectiveness and safety of prophylactic ALT in cancer patients with CVCs. A literature search was performed using the Medline database and Google Scholar from inception until April 2016. The following terms were used: 'antimicrobial lock solution', 'antibiotic lock solution', 'oncology', 'hematology', 'pediatrics', 'prevention', 'cancer', 'catheter related bloodstream infections', 'central-line associated bloodstream infection' (CLABSI) and 'central venous catheter'. Studies evaluating prophylactic ALT in cancer patients alone were eligible for inclusion. Case reports, case series and in-vitro studies were excluded. In total, 78 articles were identified. Following all exclusions, 13 articles (three adult and 10 pediatric) were selected for evaluation. The most common agents utilized were vancomycin with heparin; ethanol; taurolidine; and minocycline with EDTA. Quality of evidence was moderate to high in adult studies and low to moderate in pediatric studies. Use of ALT decreased the incidence of CLABSI in the majority of studies; however, there were significant differences in definitions of CVC-related infection, dwell times and lock solutions. Lock therapy may be an adjunct in high-risk cancer patients for the prevention of CLABSI; higher quality evidence is needed for specific ALT recommendations. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Mesoporous silica nanoparticles decorated with polycationic dendrimers for infection treatment.

PubMed

González, Blanca; Colilla, Montserrat; Díez, Jaime; Pedraza, Daniel; Guembe, Marta; Izquierdo-Barba, Isabel; Vallet-Regí, María

2018-03-01

This work aims to provide an effective and novel solution for the treatment of infection by using nanovehicles loaded with antibiotics capable of penetrating the bacterial wall, thus increasing the antimicrobial effectiveness. These nanosystems, named "nanoantibiotics", are composed of mesoporous silica nanoparticles (MSNs), which act as nanocarriers of an antimicrobial agent (levofloxacin, LEVO) localized inside the mesopores. To provide the nanosystem of bacterial membrane interaction capability, a polycationic dendrimer, concretely the poly(propyleneimine) dendrimer of third generation (G3), was covalently grafted to the external surface of the LEVO-loaded MSNs. After physicochemical characterization of this nanoantibiotic, the release kinetics of LEVO and the antimicrobial efficacy of each released dosage were evaluated. Besides, internalization studies of the MSNs functionalized with the G3 dendrimer were carried out, showing a high penetrability throughout Gram-negative bacterial membranes. This work evidences that the synergistic combination of polycationic dendrimers as bacterial membrane permeabilization agents with LEVO-loaded MSNs triggers an efficient antimicrobial effect on Gram-negative bacterial biofilm. These positive results open up very promising expectations for their potential application in new infection therapies. Seeking new alternatives to current available treatments of bacterial infections represents a great challenge in nanomedicine. This work reports the design and optimization of a new class of antimicrobial agent, named "nanoantibiotic", based on mesoporous silica nanoparticles (MSNs) decorated with polypropyleneimine dendrimers of third generation (G3) and loaded with levofloxacin (LEVO) antibiotic. The covalently grafting of these G3 dendrimers to MSNs allows an effective internalization in Gram-negative bacteria. Furthermore, the LEVO loaded into the mesoporous cavities is released in a sustained manner at effective antimicrobial dosages. The novelty and originality of this manuscript relies on proving that the synergistic combination of bacteria-targeting and antimicrobial agents into a unique nanosystem provokes a remarkable antimicrobial effect against bacterial biofilm. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Lymphocyte function following radioiodine therapy in patients with thyroid carcinoma.

PubMed

Barsegian, V; Müller, S P; Horn, P A; Bockisch, A; Lindemann, M

2011-01-01

Since the nuclear disaster in Fukushima has raised great concern about the danger of radioactivity, we here addressed the question if the therapeutic use of iodine 131, the most frequently applied radionuclide, was harmful to immune function in patients. It was our aim to define for the first time in a clinical setting how radioiodine therapy alters anti-microbial immune responses. In 21 patients with thyroid carcinoma anti-microbial lymphocyte responses were assessed by lymphocyte transformation test and ELISpot - measuring lymphocyte proliferation and on a single cell level production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) - prior to therapy, at day 1 and day 7 post therapy. Proliferative lymphocyte responses and interferon-γ production after in vitro stimulation with microbial antigens were significantly (p < 0.05) increased at day 1 vs. pre therapy, and returned to pre therapy levels at day 7. On the contrary, at day 1 interleukin-10 production was significantly (p < 0.05) reduced. Thus, we observed a short-term increase in pro-inflammatory immune responses. However, T lymphocyte responses were in the range of healthy controls at all three time points. Thyroid carcinoma patients receiving radioiodine therapy do not display any sign of immunosuppression.

[Blood culture negative endocarditis: a diagnostic challenge].

PubMed

Wälli, F; Chuard, C; Regamey, C

2005-10-12

Blood culture negative endocarditis (BCNE) account for about 5% of all cases of endocarditis. Diagnosis and initiation of antimicrobial therapy may be delayed, with a negative impact on clinical outcome. The most common cause of BCNE is antimicrobial drug therapy before blood sampling. Other common causes include slow growing and non cultivable organisms. Identification of the etiologic agent is critical in the management of BCNE and molecular tools such as broad range 16SrRNA PCR technique followed by direct automated sequencing and microorganism-specific PCR are promising. Some authors have proposed to include these techniques among major Duke's criteria for the diagnosis of BCNE.

Effects of antimicrobial therapy on faecal bulking.

PubMed Central

Kurpad, A V; Shetty, P S

1986-01-01

It has recently been postulated that dietary fibre acts as a substrate for colonic flora, and that the resultant microbial growth bulks the faeces. Antimicrobial therapy was used in this study to assess the effect of reduction in colonic microbial proliferation on faecal output in human subjects on a constant dietary fibre intake. Six healthy young male subjects were maintained on constant daily diets and metronidazole (1 g/day) and ampicillin (1 g/day) were administered in divided doses for one week after an initial baseline study period of two weeks. After antimicrobial therapy, mean faecal weights rose from 176.0 +/- 27.0 g to 348.1 +/- 37.7 g/day. Faecal solids increased from 32.9 +/- 4.2 g to 46.1 +/- 5.8 g/day. Faecal neutral detergent fibre increased from 1.92 +/- 0.42 g to 15.19 +/- 2.58 g/day. The mean transit times and mean daily faecal nitrogen remained the same, both before and after treatment. Substantial breakdown of dietary fibre occurs in the human colon which may decrease faecal bulk, suggesting that water holding by dietary fibre is probably of greater importance for faecal bulking. PMID:3005139

Trends in antibiotic resistance over time among pathogens from Canadian hospitals: results of the CANWARD study 2007-11.

PubMed

Lagacé-Wiens, Philippe R S; Adam, Heather J; Low, Donald E; Blondeau, Joseph M; Baxter, Melanie R; Denisuik, Andrew J; Nichol, Kimberly A; Walkty, Andrew; Karlowsky, James A; Mulvey, Michael R; Hoban, Daryl J; Zhanel, George G

2013-05-01

Antimicrobial resistance patterns change over time and longitudinal surveillance studies provide insight into these trends. We sought to describe the important trends in antimicrobial resistance in key pathogens across Canada to provide useful information to clinicians, policy makers and industry, to assist in optimizing antimicrobial therapy, formulary choices and drug development. We analysed longitudinal data from the CANWARD study using a multivariate regression model to control for possible effects of patient demographics on resistance, in order to assess the impact of time on antimicrobial resistance independent of other measured variables. We identified several key trends in common pathogens. In particular, we observed a statistically significant increase in the proportion of Escherichia coli isolates that were resistant to extended-spectrum cephalosporins and fluoroquinolones, an increase in the proportion of Klebsiella pneumoniae isolates that were resistant to extended-spectrum cephalosporins, a reduction in the proportion of Staphylococcus aureus that were methicillin, clindamycin and trimethoprim/sulfamethoxazole resistant, and a reduction in the proportion of Pseudomonas aeruginosa that were fluoroquinolone and gentamicin resistant. Although some of these trends, such as the dramatic increase in fluoroquinolone and cephalosporin resistance in E. coli, can be attributed to the emergence and global spread of resistant clones (e.g. ST131 E. coli), others remain unexplained. However, recognizing these trends remains important to guide changes in empirical antimicrobial therapy and drug development.

Topical Antimicrobials for Burn Wound Infections

PubMed Central

Dai, Tianhong; Huang, Ying-Ying; Sharma, Sulbha K.; Hashmi, Javad T.; Kurup, Divya B.; Hamblin, Michael R.

2010-01-01

Throughout most of history, serious burns occupying a large percentage of body surface area were an almost certain death sentence because of subsequent infection. A number of factors such as disruption of the skin barrier, ready availability of bacterial nutrients in the burn milieu, destruction of the vascular supply to the burned skin, and systemic disturbances lead to immunosuppression combined together to make burns particularly susceptible to infection. In the 20th century the introduction of antibiotic and antifungal drugs, the use of topical antimicrobials that could be applied to burns, and widespread adoption of early excision and grafting all helped to dramatically increase survival. However the relentless increase in microbial resistance to antibiotics and other antimicrobials has led to a renewed search for alternative approaches to prevent and combat burn infections. This review will cover patented strategies that have been issued or filed with regard to new topical agents, preparations, and methods of combating burn infections. Animal models that are used in preclinical studies are discussed. Various silver preparations (nanocrystalline and slow release) are the mainstay of many approaches but antimicrobial peptides, topical photodynamic therapy, chitosan preparations, new iodine delivery formulations, phage therapy and natural products such as honey and essential oils have all been tested. This active area of research will continue to provide new topical antimicrobials for burns that will battle against growing multi-drug resistance. PMID:20429870

Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014-2016: Study for monitoring antimicrobial resistance trend report.

PubMed

Veeraraghavan, Balaji; Jesudason, Mark Ranjan; Prakasah, John Antony Jude; Anandan, Shalini; Sahni, Rani Diana; Pragasam, Agila Kumari; Bakthavatchalam, Yamuna Devi; Selvakumar, Rajesh Joseph; Dhole, T N; Rodrigues, Camilla; Roy, Indranil; Joshi, Sangeetha; Chaudhuri, Bhaskar Narayan; Chitnis, D S

2018-01-01

The emergence of antibiotic resistance among bacterial pathogens in the hospital and community has increased the concern to the health-care providers due to the limited treatment options. Surveillance of antimicrobial resistance (AMR) in frequently isolated bacterial pathogens causing severe infections is of great importance. The data generated will be useful for the clinicians to decide empiric therapy on the local epidemiological resistance profile of the antimicrobial agents. This study aims to monitor the distribution of bacterial pathogen and their susceptibility pattern to the commonly used antimicrobial agents. This study includes Gram-negative bacilli collected from intra-abdominal, urinary tract and respiratory tract infections during 2014-2016. Isolates were collected from seven hospitals across India. All the study isolates were characterised up to species level, and minimum inhibitory concentration was determined for a wide range of antimicrobials included in the study panel. The test results were interpreted as per standard Clinical Laboratory Standards Institute guidelines. A total of 2731 isolates of gram-negative bacteria were tested during study period. The most frequently isolated pathogens were 44% of Escherichia coli (n = 1205) followed by 25% of Klebsiella pneumoniae (n = 676) and 11% of Pseudomonas aeruginosa (n = 308). Among the antimicrobials tested, carbapenems were the most active, followed by amikacin and piperacillin/tazobactam. The rate of extended-spectrum beta-lactamase (ESBL)-positive isolates were ranged from 66%-77% in E. coli to 61%-72% in K. pneumoniae, respectively. Overall, colistin retains its activity in > 90% of the isolates tested and appear promising. Increasing rates of ESBL producers have been noted, which is alarming. Further, carbapenem resistance was also gradually increasing, which needs much attention. Overall, this study data show that carbapenems, amikacin and colistin continue to be the best agents available to treat drug-resistant infections. Thus continuous monitoring of susceptibility profile of the clinically important Gram-negative pathogens is of great importance to guide effective antimicrobial therapy.

Potential Negative Effects of Antimicrobial Allergy Labelling on Patient Care: A Systematic Review.

PubMed

Wu, Julie Hui-Chih; Langford, Bradley J; Schwartz, Kevin L; Zvonar, Rosemary; Raybardhan, Sumit; Leung, Valerie; Garber, Gary

2018-01-01

Antimicrobial allergy labels, either self-reported or placed in a patient's medical record, are common, but in many cases they are not associated with a true immunoglobulin E-mediated allergic response. To assess the impact of antimicrobial allergy labels on antimicrobial prescribing, resource utilization, and clinical outcomes. The MEDLINE, Embase, CINAHL, and Scopus electronic databases were searched for the period 1990 to January 2016. Controlled studies with the objective of assessing antimicrobial prescribing, resource utilization, and/or clinical outcomes associated with antimicrobial allergy labels were included. The search identified 560 unique citations, of which 7 articles met the inclusion criteria. One additional article identified by an expert in the field was also included. Four of the identified papers were limited to penicillin or other β-lactam allergies. Six studies noted differences in antibiotic selection between patients with allergy labels and those without such labels. Broader-spectrum or second-line agents (e.g., vancomycin, clindamycin, and fluoroquinolones) were more commonly prescribed for patients with penicillin allergy labels. Antibiotic therapy costs were significantly higher for patients with allergy labels than for those without. The impact of allergy labels on clinical outcomes was mixed. One study indicated a longer length of hospital stay, 2 studies reported higher readmission rates, and 1 study reported a higher rate of antibiotic-resistant organisms for patients with allergy labels. Most of the available literature is limited to penicillin or β-lactam allergy. The growing body of knowledge supports the concept that β-lactam allergy labels are not benign and that labelling in the absence of a true allergy has a negative effect on patient care. Allergy labelling appears to be associated with suboptimal antibiotic selection, greater treatment costs, prolonged length of stay, greater readmission rates, and higher prevalence of antibiotic-resistant organisms. There is an opportunity for antimicrobial stewardship programs to implement systematic allergy verification to optimize antimicrobial therapy and improve patient care.

Antimicrobial Resistance of Urinary Tract Isolates in Acute Uncomplicated Cystitis among College-Aged Women: Choosing a First-Line Therapy

ERIC Educational Resources Information Center

Hames, Leesa; Rice, Craig E.

2007-01-01

Objective and Participants: The authors of this retrospective case study focused on antimicrobial susceptibility of urinary tract isolates in cases of acute uncomplicated cystitis in college-aged women, aged 18 to 24 years, diagnosed at a major south-central university student health center. Methods: The authors obtained pertinent data from…

Impact of Acinetobacter infection on the Mortality of Burn Patients

DTIC Science & Technology

2006-10-01

associated with in- creased mortality (Table 3). Most of the Acb isolates seen were resistant to a broad range of antimicrobials (Table 4). Imipenem ...infected patients received effec- tive therapy, as defined previously. The majority of these patients (32) received imipenem -cilastatin. Other...Antimicrobial % of isolates susceptible Imipenem 61 Amikacin 36 Ampicillin-sulbactam (n 58) 24 Tobramycin 22 Piperacillin-tazobactam 14

Triple antimicrobial therapy and acid suppression in dogs with chronic vomiting and gastric Helicobacter spp.

PubMed

Leib, Michael S; Duncan, Robert B; Ward, Daniel L

2007-01-01

Helicobacter pylori is a common cause of gastritis and peptic ulcers in humans. Many dogs, including those with gastritis and chronic vomiting, are infected with Helicobacter spp. Triple antimicrobial therapy will eradicate Helicobacter infection, improve gastritis, and reduce clinical signs. The addition of acid suppression medication will not improve results. Twenty-four pet dogs with chronic vomiting and gastric Helicobacter spp. Dogs were randomly assigned to triple antimicrobial therapy with or without famotidine. Gastroduodenoscopy was performed 4 weeks and 6 months after therapy. Helicobacter spp status was determined by histologic assessment of gastric mucosal biopsy specimens. Eradication rates for each treatment were not significantly different and combined were 75 and 42.9% at 4 weeks and 6 months, respectively. A greater improvement in gastritis scores occurred in dogs that became Helicobacter spp negative. Overall, the frequency of vomiting was reduced by 86.4%, but there were no differences between treatments. Eradication rates of Helicobacter spp with both treatments were not significantly different. Eradication rates at 6 months were modest, and more effective treatments should be developed. Acid suppression is not a necessary component of treatment protocols for dogs. Eradication of gastric Helicobacter spp was associated with improvement in gastritis scores. Dramatic reduction of the vomiting frequency occurred with both treatment protocols. Gastric Helicobacter spp may cause or contribute to chronic vomiting and gastritis in some dogs.

Infants under two months of age with urinary tract infections are showing increasing resistance to empirical and oral antibiotics.

PubMed

Segal, Zvi; Cohen, Matan J; Engelhard, Dan; Tenenbaum, Ariel; Simckes, Ari M; Benenson, Shmuel; Stepensky, Polina; Averbuch, Diana

2016-04-01

Data on antimicrobial resistance in uropathogens in infants up to the age of three months are limited. This study characterised resistance patterns in Gram-negative uropathogens in infants up to the age of two months. Previously healthy young infants with urinary tract infections (UTIs) were studied retrospectively. Antimicrobial susceptibility was evaluated. Multidrug resistance (MDR) was defined as resistance to at least three antibiotic classes. Clinical, laboratory and outcome data were compared between infants with UTIs caused by bacteria sensitive and resistant to empirical and to oral therapy. We evaluated 306 UTI episodes with 314 pathogens. The following resistance rates were observed: ampicillin 73.7%, cefazoline 22.1%, ampicillin/clavulanate 21.8%, cefuroxime 7.8%, gentamicin 7%; MDR 11.8%; resistant to empirical treatment 7.3% and resistant to available oral antibiotics 8.6%. Our study showed that pathogens resistant to empirical and oral therapy were more frequently isolated in non-Jewish (Arab) infants and in those of ≥30 days of age. Resistance to empirical treatment and oral antibiotics also resulted in longer mean hospital stays. Resistance to antibiotics challenges empirical therapy and compromises oral treatment options in young infants with UTIs. Antimicrobial resistance patterns should be monitored in infants to determine appropriate empirical antibiotic therapy protocols. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Clinical diagnosis of sepsis and the combined use of biomarkers and culture- and non-culture-based assays.

PubMed

Bloos, Frank

2015-01-01

Sepsis is among the most common causes of death in hospitalized patients, and early recognition followed by immediate initiation of therapy is an important concept to improve survival in these patients. According to the definition of sepsis, diagnosis of sepsis requires the recognition of the systemic inflammatory response syndrome (SIRS) caused by infection as well as recognition of possible infection-related organ dysfunctions for diagnosis of severe sepsis or septic shock. Both SIRS and organ dysfunctions may occur frequently in hospitalized patients for various reasons. However, the fast recognition of acute infection as a cause of SIRS and newly developed organ dysfunction may be a demanding task since culture-based results of microbiological samples will be available only days after onset of symptoms. Biomarkers and PCR-based pathogen detection may help the physician in differentiating SIRS from sepsis. Procalcitonin (PCT) is the best investigated biomarker for this purpose. Furthermore, the current data support the usage of PCT for guidance of antimicrobial therapy. C-reactive protein (CRP) may be used to monitor the course of infection but has only limited discriminative capabilities. Interleukin-6 is widely used for its fast response to the infectious stimulus, but conclusive data for the application of this biomarker are missing. None of the available biomarkers can by itself reliably differentiate SIRS from sepsis but can aid and shorten the decision process. PCR-based pathogen detection can theoretically shorten the recognition of the underlying pathogen to about 8 h. However, this technique is expensive and requires additional staff in the laboratory; controlled prospective studies are missing. Although current studies suggest that PCR-based pathogen detection may be useful to shorten time to adequate antimicrobial therapy and diagnose invasive Candida infections, no general recommendations about the application of PCR for the diagnosis of sepsis can be given.

Residual antibacterial activity of dog hairs after therapy with antimicrobial shampoos.

PubMed

Kloos, Isabell; Straubinger, Reinhard K; Werckenthin, Christiane; Mueller, Ralf S

2013-04-01

Topical antimicrobial treatment for canine pyoderma is becoming increasingly important, but little is known about the mechanism of action and persistence of activity of antimicrobial shampoos. To determine the residual antimicrobial activity on canine hairs treated with antimicrobial shampoos. Forty-two dogs from a research institution. Dogs were treated with six different shampoos and the combination of one shampoo and conditioner containing benzoyl peroxide, chlorhexidine in different concentrations (0.8, 2, 3 and 4%), ethyl lactate and miconazole twice weekly for 2 weeks. A shampoo vehicle without antimicrobial ingredients was used as the control. Hairs were collected immediately after and 2, 4 and 7 days after the last shampoo therapy and placed onto an agar plate streaked with Staphylococcus pseudintermedius. After incubation, the growth inhibition zone around the hair shafts was measured. The largest zone of inhibition of bacterial growth was seen after shampoos containing 2 and 3% chlorhexidine and the combination of chlorhexidine shampoo and conditioner. The zone of inhibition was smaller with the shampoos containing 0.8 and 4% chlorhexidine. There was no difference between the inhibition zones post-treatment with benzoyl peroxide, ethyl lactate and control. The efficacy of a shampoo is dependent not only on the concentration of the active ingredients but also on the shampoo formulation. Hair shafts treated with shampoos containing 2 and 3% chlorhexidine and the combination of shampoo and conditioner inhibited bacterial growth significantly and seem suitable to treat canine bacterial pyoderma. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

Sonodynamic inactivation of Gram-positive and Gram-negative bacteria using a Rose Bengal-antimicrobial peptide conjugate.

PubMed

Costley, David; Nesbitt, Heather; Ternan, Nigel; Dooley, James; Huang, Ying-Ying; Hamblin, Michael R; McHale, Anthony P; Callan, John F

2017-01-01

Combating antimicrobial resistance is one of the most serious public health challenges facing society today. The development of new antibiotics or alternative techniques that can help combat antimicrobial resistance is being prioritised by many governments and stakeholders across the globe. Antimicrobial photodynamic therapy is one such technique that has received considerable attention but is limited by the inability of light to penetrate through human tissue, reducing its effectiveness when used to treat deep-seated infections. The related technique sonodynamic therapy (SDT) has the potential to overcome this limitation given the ability of low-intensity ultrasound to penetrate human tissue. In this study, a Rose Bengal-antimicrobial peptide conjugate was prepared for use in antimicrobial SDT (ASDT). When Staphylococcus aureus and Pseudomonas aeruginosa planktonic cultures were treated with the conjugate and subsequently exposed to ultrasound, 5 log and 7 log reductions, respectively, in bacterial numbers were observed. The conjugate also displayed improved uptake by bacterial cells compared with a mammalian cell line (P ≤ 0.01), whilst pre-treatment of a P. aeruginosa biofilm with ultrasound resulted in a 2.6-fold improvement in sensitiser diffusion (P ≤ 0.01). A preliminary in vivo experiment involving ASDT treatment of P. aeruginosa-infected wounds in mice demonstrated that ultrasound irradiation of conjugate-treated wounds affects a substantial reduction in bacterial burden. Combined, the results obtained from this study highlight ASDT as a targeted broad-spectrum novel modality with potential for the treatment of deep-seated bacterial infections. Copyright © 2016. Published by Elsevier B.V.

Ciprofloxacin-Resistant Aeromonas hydrophila Cellulitis following Leech Therapy

PubMed Central

Giltner, Carmen L.; Bobenchik, April M.; Uslan, Daniel Z.; Deville, Jaime G.

2013-01-01

We report a case of surgical site infection with ciprofloxacin-resistant Aeromonas hydrophila following leech therapy. Antimicrobial and genetic analyses of leech and patient isolates demonstrated that the resistant isolates originated from the leech gut microbiota. These data suggest that ciprofloxacin monotherapy as a prophylaxis regimen prior to leech therapy may not be effective in preventing infection. PMID:23363826

Treatment of mastitis in cattle.

PubMed

Royster, Erin; Wagner, Sarah

2015-03-01

The understanding of mastitis, its cause, and the rationale for treatment or nontreatment of mastitis under various circumstances continues to evolve. This article presents research-based evidence about the use or nonuse of drugs to treat mastitis. Nondrug factors involved in decision making about mastitis, including cow characteristics and the epidemiology of mastitis, are also briefly discussed. This article provides information that helps in the making of knowledgeable, evidence-based decisions about therapy for mastitis. Focus is primarily on the use of antimicrobial drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-microbial resistance stratified by risk factor among Escherichia coli strains isolated from the urinary tract at a rural clinic in Central India.

PubMed

Chatterjee, B; Kulathinal, S; Bhargava, A; Jain, Y; Kataria, R

2009-01-01

The failure of empirical therapy is frequently observed, even in community-acquired urinary tract infections. We, therefore, conducted a prospective, clinic-based study in 2004-2005 to document anti-microbial resistance rates and correlate them with possible risk factors to assist empirical decision-making. Symptomatic patients with pyuria underwent urine culture. Isolates were identified using standard methods and anti-microbial resistance was determined by disk-diffusion. Ultrasonography was used to detect complicating factors. Patients were stratified by the presence of complicating factors and history of invasive procedures for comparison of resistance rates. STATISTICAL METHOD USED: Chi-square or Fisher exact tests, as appropriate. There were 156 E. coli isolates, of which 105 were community-acquired. Twenty-three community-acquired isolates were from patients with complicating factors while 82 were from patients without any. Fifty-one isolates were from patients who had recently undergone invasive procedures on the urinary tract. Thirty-two community-acquired isolates from reproductive-age women without apparent complicating factors had resistance rates of 50% or above against tetracyclines, Co-trimoxazole, aminopenicillins, Nalidixic acid, Ciprofloxacin and 1 st generation cephalosporins. Resistance rates were significantly higher among isolates from patients subjected to invasive procedures, except against Co-trimoxazole, tetracyclines and Amikacin. High rates of anti-microbial resistance in community-acquired uropathogens have made antimicrobial sensitivity testing necessary even in a rural, primary-care setting.

New photosensitive nanometric graphite oxide composites as antimicrobial material with prolonged action.

PubMed

Gerasymchuk, Y; Lukowiak, A; Wedzynska, A; Kedziora, A; Bugla-Ploskonska, G; Piatek, D; Bachanek, T; Chernii, V; Tomachynski, L; Strek, W

2016-06-01

A new conjugate material based on partially reduced graphite oxide (rGO), silver nanoparticles (Ag), and bis(lysinato)zirconium(IV) phthalocyanine complex (ZrPc) was obtained. Its optical properties (absorption and photoluminescence) after dispersion in solvents were examined. The antimicrobial properties were tested to determine the effect of the composite on the following bacterial strains: Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, which are responsible for many infections and are one of the pathogens the most difficult to treatment. The results obtained for rGO-ZrPc-Ag composite were compared with the properties of GO, GO-ZrPc, and rGO-Ag structures. The influence of the near-infrared irradiation on the antimicrobial activity of ZrPc- and Ag-doped materials against bacteria was observed for very low concentration (0.32mg/mL) of GO-ZrPc to stop the growth of P. aeruginosa in comparison to the nonirradiated sample (41mg/mL). The usefulness of this material in therapy, such as wound infection treatment or endodontic treatment, as antibacterial agent with sustained action was discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Genome Expression Profiling-Based Identification and Administration Efficacy of Host-Directed Antimicrobial Drugs against Respiratory Infection by Nontypeable Haemophilus influenzae

PubMed Central

Euba, Begoña; Moleres, Javier; Segura, Víctor; Viadas, Cristina; Morey, Pau; Moranta, David; Leiva, José; de-Torres, Juan Pablo; Bengoechea, José Antonio

2015-01-01

Therapies that are safe, effective, and not vulnerable to developing resistance are highly desirable to counteract bacterial infections. Host-directed therapeutics is an antimicrobial approach alternative to conventional antibiotics based on perturbing host pathways subverted by pathogens during their life cycle by using host-directed drugs. In this study, we identified and evaluated the efficacy of a panel of host-directed drugs against respiratory infection by nontypeable Haemophilus influenzae (NTHi). NTHi is an opportunistic pathogen that is an important cause of exacerbation of chronic obstructive pulmonary disease (COPD). We screened for host genes differentially expressed upon infection by the clinical isolate NTHi375 by analyzing cell whole-genome expression profiling and identified a repertoire of host target candidates that were pharmacologically modulated. Based on the proposed relationship between NTHi intracellular location and persistence, we hypothesized that drugs perturbing host pathways used by NTHi to enter epithelial cells could have antimicrobial potential against NTHi infection. Interfering drugs were tested for their effects on bacterial and cellular viability, on NTHi-epithelial cell interplay, and on mouse pulmonary infection. Glucocorticoids and statins lacked in vitro and/or in vivo efficacy. Conversely, the sirtuin-1 activator resveratrol showed a bactericidal effect against NTHi, and the PDE4 inhibitor rolipram showed therapeutic efficacy by lowering NTHi375 counts intracellularly and in the lungs of infected mice. PDE4 inhibition is currently prescribed in COPD, and resveratrol is an attractive geroprotector for COPD treatment. Together, these results expand our knowledge of NTHi-triggered host subversion and frame the antimicrobial potential of rolipram and resveratrol against NTHi respiratory infection. PMID:26416856

Nafcillin enhances innate immune-mediated killing of methicillin-resistant Staphylococcus aureus.

PubMed

Sakoulas, George; Okumura, Cheryl Y; Thienphrapa, Wdee; Olson, Joshua; Nonejuie, Poochit; Dam, Quang; Dhand, Abhay; Pogliano, Joseph; Yeaman, Michael R; Hensler, Mary E; Bayer, Arnold S; Nizet, Victor

2014-02-01

Based on in vitro synergy studies, the addition of nafcillin to daptomycin was used to treat refractory methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Daptomycin is a de facto cationic antimicrobial peptide in vivo, with antistaphylococcal mechanisms reminiscent of innate host defense peptides (HDPs). In this study, the effects of nafcillin on HDP activity against MRSA were examined in vitro and in vivo. Exposures to β-lactam antimicrobials in general, and nafcillin in particular, significantly increased killing of S. aureus by selected HDPs from keratinocytes, neutrophils, and platelets. This finding correlated with enhanced killing of MRSA by whole blood, neutrophils, and keratinocytes after growth in nafcillin. Finally, nafcillin pretreatment ex vivo reduced MRSA virulence in a murine subcutaneous infection model. Despite the lack of direct activity against MRSA, these studies show potent, consistent, and generalized nafcillin-mediated "sensitization" to increased killing of MRSA by various components of the innate host response. The use of nafcillin as adjunctive therapy in MRSA bacteremia merits further study and should be considered in cases refractory to standard therapy. Nafcillin has been used as adjunctive therapy to clear persistent MRSA bacteremia. Nafcillin enhances killing of MRSA by a cadre of innate host defense peptides. Nafcillin increases binding of human cathelicidin LL-37 to the MRSA membrane. Nafcillin enhances killing of MRSA by neutrophils. Nafcillin reduces virulence of MRSA in a murine subcutaneous infection model.

Association of Inpatient Antimicrobial Utilization Measures with Antimicrobial Stewardship Activities and Facility Characteristics of Veterans Affairs Medical Centers.

PubMed

Graber, Christopher J; Jones, Makoto M; Chou, Ann F; Zhang, Yue; Goetz, Matthew Bidwell; Madaras-Kelly, Karl; Samore, Matthew H; Glassman, Peter A

2017-05-01

Antimicrobial stewardship programs (ASPs) have been advocated to improve antimicrobial utilization, but program implementation is variable. Antimicrobial stewardship programs (ASPs) have been advocated to improve antimicrobial utilization, but program implementation is variable. To determine associations between ASPs and facility characteristics, and inpatient antimicrobial utilization measures in the Veterans Affairs (VA) system in 2012. In 2012, VA administered a survey on antimicrobial stewardship practices to designated ASP contacts at VA acute care hospitals. From the survey, we identified 34 variables across 3 domains (evidence, organizational context, and facilitation) that were assessed using multivariable least absolute shrinkage and selection operator regression against 4 antimicrobial utilization measures from 2012: aggregate acute care antimicrobial use, antimicrobial use in patients with non-infectious primary discharge diagnoses, missed opportunities to convert from parenteral to oral antimicrobial therapy, and double anaerobic coverage. All 130 VA facilities with acute care services. Variables associated with at least 3 favorable changes in antimicrobial utilization included presence of postgraduate physician/pharmacy training programs, number of antimicrobial-specific order sets, frequency of systematic de-escalation review, presence of pharmacists and/or infectious diseases (ID) attendings on acute care ward teams, and formal ID training of the lead ASP pharmacist. Variables associated with 2 unfavorable measures included bed size, the level of engagement with VA Antimicrobial Stewardship Task Force online resources, and utilization of antimicrobial stop orders. Formalization of ASP processes and presence of pharmacy and ID expertise are associated with favorable utilization. Systematic de-escalation review and order set establishment may be high-yield interventions. Journal of Hospital Medicine 2017;12:301-309. © 2017 Society of Hospital Medicine

Quality of antimicrobial drug prescription in hospital.

PubMed

van der Meer, J W; Gyssens, I C

2001-01-01

There is worldwide concern about the development of antimicrobial resistance [1]. Selective pressure by antimicrobial drugs is by far the most important driving force for the development of resistance. Antimicrobial drugs are among the most commonly prescribed drugs in hospitals. In developed countries, some 30% of the hospitalized patients will be treated with these drugs. It is generally accepted that antimicrobial prescribing is often suboptimal, even in a country like the Netherlands, where both antibiotic consumption and microbial resistance rates are low [2,3]. The major problem with inappropriate prescribing is because of insufficient education in infectious diseases and antimicrobial therapy. Often, the prescription of these drugs with little toxicity is unjustified because of insecurity about the diagnosis of the clinician; 'drugs of fear' [4]. In our surveys, some 15% of the antibiotic prescriptions in surgical and internal medicine wards were considered unjustified [5,6]. Many prescribers are not yet fully aware that their justified or unjustified prescription adds to the resistance problem. In this paper, aspects of the quality of antimicrobial prescribing in the hospital setting will be discussed.

Current Advances in the Antimicrobial Potential of Species of Genus Ganoderma (Higher Basidiomycetes) against Human Pathogenic Microorganisms (Review).

PubMed

Rai, Mahendra K; Gaikwad, Swapnil; Nagaonkar, Dipali; dos Santos, Carolina Alves

2015-01-01

Ganoderma spp. are very important therapeutic mushrooms and have been used traditionally for 4000 years in the treatment of various human disorders. Different species of Ganoderma possess bioactive compounds, which have already demonstrated antiviral, antibacterial, and antifungal activities. Various bioactive compounds such as triterpenoids, colossolactones, and polysaccharides, which are responsible for the antimicrobial potential of the genus, are discussed here in detail. Some Ganoderma spp. have been reported to be potential agents for the synthesis of metal nanoparticles. These nanoparticles have demonstrated antimicrobial activity and also are reviewed herein. The main aim of this review is to discuss the possible use of Ganoderma extracts and their active principles in antimicrobial therapy.

Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

PubMed

Rahme, Christine; Butterfield, Jill M; Nicasio, Anthony M; Lodise, Thomas P

2014-12-01

We are rapidly approaching a crisis in antibiotic resistance, particularly among Gram-negative pathogens. This, coupled with the slow development of novel antimicrobial agents, underscores the exigency of redeploying existing antimicrobial agents in innovative ways. One therapeutic approach that was heavily studied in the 1980s but abandoned over time is dual beta-lactam therapy. This article reviews the evidence for combination beta-lactam therapy. Overall, in vitro, animal and clinical data are positive and suggest that beta-lactam combinations produce a synergistic effect against Gram-negative pathogens that rivals that of beta-lactam-aminoglycoside or beta-lactam-fluoroquinolone combination therapy. Although the precise mechanism of improved activity is not completely understood, it is likely attributable to an enhanced affinity to the diverse penicillin-binding proteins found among Gram negatives. The collective data indicate that dual beta-lactam therapy should be revisited for serious Gram-negative infections, especially in light of the near availability of potent beta-lactamase inhibitors, which neutralize the effect of problematic beta-lactamases. Copyright © 2014 Elsevier Inc. All rights reserved.

Graphene quantum dots with nitrogen-doped content dependence for highly efficient dual-modality photodynamic antimicrobial therapy and bioimaging.

PubMed

Kuo, Wen-Shuo; Chen, Hua-Han; Chen, Shih-Yao; Chang, Chia-Yuan; Chen, Pei-Chi; Hou, Yung-I; Shao, Yu-Ting; Kao, Hui-Fang; Lilian Hsu, Chih-Li; Chen, Yi-Chun; Chen, Shean-Jen; Wu, Shang-Rung; Wang, Jiu-Yao

2017-03-01

Reactive oxygen species is the main contributor to photodynamic therapy. The results of this study show that a nitrogen-doped graphene quantum dot, serving as a photosensitizer, was capable of generating a higher amount of reactive oxygen species than a nitrogen-free graphene quantum dot in photodynamic therapy when photoexcited for only 3 min of 670 nm laser exposure (0.1 W cm -2 ), indicating highly improved antimicrobial effects. In addition, we found that higher nitrogen-bonding compositions of graphene quantum dots more efficiently performed photodynamic therapy actions than did the lower compositions that underwent identical treatments. Furthermore, the intrinsically emitted luminescence from nitrogen-doped graphene quantum dots and high photostability simultaneously enabled it to act as a promising contrast probe for tracking and localizing bacteria in biomedical imaging. Thus, the dual modality of nitrogen-doped graphene quantum dots presents possibilities for future clinical applications, and in particular multidrug resistant bacteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

A 96-well-plate-based optical method for the quantitative and qualitative evaluation of Pseudomonas aeruginosa biofilm formation and its application to susceptibility testing.

PubMed

Müsken, Mathias; Di Fiore, Stefano; Römling, Ute; Häussler, Susanne

2010-08-01

A major reason for bacterial persistence during chronic infections is the survival of bacteria within biofilm structures, which protect cells from environmental stresses, host immune responses and antimicrobial therapy. Thus, there is concern that laboratory methods developed to measure the antibiotic susceptibility of planktonic bacteria may not be relevant to chronic biofilm infections, and it has been suggested that alternative methods should test antibiotic susceptibility within a biofilm. In this paper, we describe a fast and reliable protocol for using 96-well microtiter plates for the formation of Pseudomonas aeruginosa biofilms; the method is easily adaptable for antimicrobial susceptibility testing. This method is based on bacterial viability staining in combination with automated confocal laser scanning microscopy. The procedure simplifies qualitative and quantitative evaluation of biofilms and has proven to be effective for standardized determination of antibiotic efficiency on P. aeruginosa biofilms. The protocol can be performed within approximately 60 h.

Antimicrobial Susceptibility Testing, Drug Resistance Mechanisms, and Therapy of Infections with Nontuberculous Mycobacteria

PubMed Central

Nash, Kevin A.; Wallace, Richard J.

2012-01-01

Summary: Within the past 10 years, treatment and diagnostic guidelines for nontuberculous mycobacteria have been recommended by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA). Moreover, the Clinical and Laboratory Standards Institute (CLSI) has published and recently (in 2011) updated recommendations including suggested antimicrobial and susceptibility breakpoints. The CLSI has also recommended the broth microdilution method as the gold standard for laboratories performing antimicrobial susceptibility testing of nontuberculous mycobacteria. This article reviews the laboratory, diagnostic, and treatment guidelines together with established and probable drug resistance mechanisms of the nontuberculous mycobacteria. PMID:22763637

Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris.

PubMed

Borovaya, Alena; Dombrowski, Yvonne; Zwicker, Stephanie; Olisova, Olga; Ruzicka, Thomas; Wolf, Ronald; Schauber, Jürgen; Sárdy, Miklós

2014-10-01

In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human β-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.

Physicians’ knowledge, perceptions, and attitudes toward antimicrobial prescribing in Riyadh, Saudi Arabia

PubMed Central

Baadani, Abeer M.; Baig, Kamran; Alfahad, Wafa A.; Aldalbahi, Sultan; Omrani, Ali S.

2015-01-01

Objectives: To assess knowledge, perceptions, and attitudes toward antimicrobial prescribing among physicians practicing in Riyadh, Saudi Arabia. Methods: A questionnaire was developed and distributed to physicians working in hospitals in Riyadh, Saudi Arabia between June and August 2013. The results were analyzed using Stata 12 software. Results: Two hundred and twelve (84.8%) full responses were returned. Most respondents perceived antimicrobial resistance as a significant problem in their daily practice (119, 56.1%) and at a national level (148, 69.8%). Inappropriate empirical therapy (101, 47.6%) and excessive use of antimicrobials in healthcare settings (66, 31.1%) were believed to be the main contributors to increasing bacterial resistance. Respondents favor treating infection rather than colonization (98, 46.2%), and physician education (74, 34.9%) as the most effective interventions to reduce antimicrobial resistance. Many respondents (95, 44.8%) do not feel confident in their knowledge of antimicrobial prescribing. Two-thirds of the respondents (135, 63.7%) have local antimicrobial guidelines, of which 90 (66.7%) felt were useful. Most respondents (160, 75.5%) considered their local infectious diseases service to be very helpful. Conclusion: There are considerable unmet training and education need for physicians in the area of antimicrobial prescribing. Local antimicrobial guidelines need revision to ensure they are more relevant and helpful for medical practitioners. PMID:25935184

A survey of veterinary antimicrobial prescribing practices, Washington State 2015.

PubMed

Fowler, H; Davis, M A; Perkins, A; Trufan, S; Joy, C; Buswell, M; McElwain, T F; Moore, D; Worhle, R; Rabinowitz, P M

2016-12-24

Antimicrobial resistance is a growing global health issue. It is also a recognised problem in veterinary medicine. Between September and December 2015 the authors administered a cross-sectional survey to licensed veterinarians in Washington State to assess factors affecting antimicrobial prescribing practices among veterinarians in Washington State. Two hundred and three veterinarians completed the survey. The majority of respondents (166, 82 per cent) were engaged in small animal or exotic animal practice. 24 per cent of respondents reported not ordering culture and sensitivity (C/S) testing in practice. Of the 76 per cent of veterinarians who reported ordering C/S tests, 36 per cent reported ordering such testing 'often' or 'always' when treating presumptive bacterial infections. Most respondents (65 per cent) mentioned cost as the most common barrier to ordering a C/S test. Only 16 (10 per cent) respondents reported having access to or utilising a clinic-specific antibiogram. This survey demonstrated that while antimicrobials are commonly used in veterinary practice, and veterinarians are concerned about antimicrobial resistance, cost is a barrier to obtaining C/S tests to guide antimicrobial therapy. Summaries of antimicrobial resistance patterns are rarely available to the practising veterinarian. Efforts to promote antimicrobial stewardship in a 'One Health' manner should address barriers to the judicious use of antimicrobials in the veterinary practice setting. British Veterinary Association.

Antimicrobial stewardship programs: interventions and associated outcomes.

PubMed

Patel, Dimple; Lawson, Wendy; Guglielmo, B Joseph

2008-04-01

Guidelines regarding antimicrobial stewardship programs recommend an infectious diseases-trained physician and an infectious diseases-trained pharmacist as core members. Inclusion of clinical microbiologists, infection-control practitioners, information systems experts and hospital epidemiologists is considered optimal. Recommended stewardship interventions include prospective audit and intervention, formulary restriction, education, guideline development, clinical pathway development, antimicrobial order forms and the de-escalation of therapy. The primary outcome associated with these interventions has been the associated cost savings; however, few published investigations have taken into account the overall cost of the intervention. Over the past 5 years, there has been an increased focus upon interventions intended to decrease bacterial resistance or reduce superinfection, including infections associated with Clostridium difficile colitis. Few programs have been associated with a reduction in antimicrobial drug adverse events. Antimicrobial stewardship programs are becoming increasingly associated with clear benefits and will be integral in the in-patient healthcare setting.

Multi drug resistance and Extended Spectrum Beta Lactamases in clinical isolates of Shigella: A study from New Delhi, India.

PubMed

Aggarwal, Prabhav; Uppal, Beena; Ghosh, Roumi; Krishna Prakash, S; Chakravarti, Anita; Jha, Arun Kumar; Rajeshwari, Krishnan

2016-01-01

Shigella is an important cause of gastroenteritis in local Indian population, as well as of traveler's diarrhea in the international visitors to India. These patients often require appropriate antimicrobial therapy; however, rapid development of antimicrobial resistance poses a major hurdle in achieving this goal. A prospective study was conducted during 2009-12 in New Delhi, India, including 6339 stool samples from gastroenteritis patients. 121 Shigella strains were identified on the basis of colony morphology, biochemical reactions, serotyping and ipaH gene based PCR. Antimicrobial susceptibility testing by disc diffusion, MIC determination by Vitek(®) 2 and phenotypic tests for ESBL/AmpC production were done. Nineteen percent strains (23/121) were found to be resistant to third generation cephalosporins and all were phenotypically confirmed to be ESBL producers; one strain was positive for AmpC. ESBL producing strains were also found to be significantly more resistant (p < 0.05) to several other antimicrobials agents in comparison to ESBL non-producers, [ampicillin (100% vs. 62.2%), ampicillin/sulbactam (100% vs. 30.6%), cotrimoxazole (100% vs. 77.6%), ciprofloxacin (87.0% vs. 49.0%), ofloxacin (87.0% vs. 52.0%) and gentamicin (30.4% vs. 7.1%)]. Multidrug resistance was seen in 76% strains. Inappropriate use of antimicrobial agents puts high selection pressure on the higher-end antibiotics. Multi-drug resistance and high rates of ESBL production by Shigella is a matter of concern for the local population as well as international travelers. Therefore, better national level antimicrobial management programs are the priority needs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preventative Therapeutics for Heterotopic Ossification

DTIC Science & Technology

2015-10-01

plastic cages and kept on a 12-hour light/dark cycle with unlimited access to food (standard rodent chow) and freshwater ad libitum. The study protocol (12...osteogenic mediators, we further propose that initiation of prophylactic local and/or systemicGram-positive antimicrobial therapy at the time of injury and...polymicrobial infections, impact of differential TLR signaling, and the evaluation of systemic and/or local antimicrobial in- terventions, is necessary

Modified Augmented Renal Clearance Score Predicts Rapid Piperacillin and Tazobactam Clearance in Critically Ill Surgery and Trauma Patients

DTIC Science & Technology

2014-04-24

intermittent dosing regimens. CONCLUSION: Given its ability to predict antimicrobial clearance above populationmedians, which could compromise therapy, the...campaign dedicated to improve out- comes.1,2 In the era ofmultiply drug- resistant pathogens and rising antimicrobial minimum inhibitory concentrations (MICs...urinary creatinine clearance significantly exceeds what is predicted by the serum creatinine concentration according to various mathematical

[Proper antibiotic therapy. From penicillin to pharmacogenomic].

PubMed

Caramia, G; Ruffini, E

2012-04-01

Antibiotics have always been considered one of the wonder discoveries of the 20th century. The use of penicillin by Flaming, opened up the golden era of antibiotics and now is hard to imagine the practice of medicine without antibiotics. Life-threatening infections, such as meningitis, endocarditis, bacteremic pneumonia sepsis, would again prove fatal. Also aggressive chemotherapy and transplant procedures would prove impossible. Another real wonder has been the rise of antibiotic resistance soon after the clinical use of penicillin in hospitals and communities. Several study demonstrated an excessive amount of antibiotic prescribing for communities patients and inpatients and in some hospital up to 50% of antibiotic usage is inappropriate: the benefits of antibiotic treatment come with the risk of antibiotic resistance development. In hospitals, infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. A variety of strategies has been proposed to reduce the cost and improve the quality of medication use. Education, guidelines and evidence based recommendations are considered to be essential elements of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies. Evidence-based recommendations, an approach to clinical practice helping to make decisions based on clinical expertise and on intimate knowledge of the individual patient's situations, beliefs, and priorities, enhance antimicrobial stewardship, that include appropriate selection, dosing, route, and duration of antimicrobial therapy can maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost. These evidence-based guidelines are not a substitute for clinical judgment, and clinical discretion is always required in their application. Genome studies have identified hundreds of genetic polymorphism important determinants of the efficacy of therapy and several trial demonstrated the successful use of pharmacogenomic testing to reduce the incidence of hypersensitivity reactions in patients. Knowing the phenotype of a patient prior to therapy, optimal dose and type drugs can be prescribed to achieve better management of patients.

Short-term versus continuous antimicrobial therapy for asymptomatic bacteriuria in pregnancy.

PubMed

Whalley, P J; Cunningham, F G

1977-03-01

Asymptomatic bacteriuria was identified in 300 pregnant women prior to the 28th week of gestation. In one group of 200 women short-term treatment with either nitrofurantoin or sulfamethizole was given for 14 days, and in another group of 100 women continuous therapy with one of these drugs was given for the remainder of gestation. Weekly urine cultures were obtained from all the women. Of the women treated with short-term therapy, 65% were abacteriuric for the remainder of pregnancy following one course of therapy, 24% became abacteriuric but subsequently relapsed, 2% had reinfection after becoming abacteriuric, and 9% demonstrated no response. Following treatment with a second course of short-term therapy, another 19% of these women were cured for the remainder of their pregnancy, and 3.5% responded to a third course. In the continuous therapy group, 88% of the women became abacteriuric for the remainder of the gestation, 3% demonstrated relapse, 2% developed reinfection, and 7% had no response to the first drug given. These data demonstrate that short-term administration of antimicrobials, when combined with surveillance for recurrent bacteriuria, is effective for the management of the pregnant woman with asymptomatic bacteriuria.

Clinical manifestations and management of left ventricular assist device-associated infections.

PubMed

Nienaber, Juhsien Jodi C; Kusne, Shimon; Riaz, Talha; Walker, Randall C; Baddour, Larry M; Wright, Alan J; Park, Soon J; Vikram, Holenarasipur R; Keating, Michael R; Arabia, Francisco A; Lahr, Brian D; Sohail, M Rizwan

2013-11-01

Infection is a serious complication of left ventricular assist device (LVAD) therapy. Published data regarding LVAD-associated infections (LVADIs) are limited by single-center experiences and use of nonstandardized definitions. We retrospectively reviewed 247 patients who underwent continuous-flow LVAD implantation from January 2005 to December 2011 at Mayo Clinic campuses in Minnesota, Arizona, and Florida. LVADIs were defined using the International Society for Heart and Lung Transplantation criteria. We identified 101 episodes of LVADI in 78 patients (32%) from this cohort. Mean age (± standard deviation [SD]) was 57±15 years. The majority (94%) underwent Heartmate II implantation, with 62% LVADs placed as destination therapy. The most common type of LVADIs were driveline infections (47%), followed by bloodstream infections (24% VAD related, and 22% non-VAD related). The most common causative pathogens included gram-positive cocci (45%), predominantly staphylococci, and nosocomial gram-negative bacilli (27%). Almost half (42%) of the patients were managed by chronic suppressive antimicrobial therapy. While 14% of the patients had intraoperative debridement, only 3 underwent complete LVAD removal. The average duration (±SD) of LVAD support was 1.5±1.0 years. At year 2 of follow-up, the cumulative incidence of all-cause mortality was estimated to be 43%. Clinical manifestations of LVADI vary on the basis of the type of infection and the causative pathogen. Mortality remained high despite combined medical and surgical intervention and chronic suppressive antimicrobial therapy. Based on clinical experiences, a management algorithm for LVADI is proposed to assist in the decision-making process.

Synthesis, bioanalysis and biodistribution of photosensitizer conjugates for photodynamic therapy

PubMed Central

Denis, Tyler GSt; Hamblin, Michael R

2013-01-01

Photodynamic therapy (PDT) was discovered in 1900 by Raab, and has since emerged as a promising tool for treating diseases characterized by unwanted cells or hyperproliferating tissue (e.g., cancer or infectious disease). PDT consists of the light excitation of a photosensitizer (PS) in the presence of O2 to yield highly reactive oxygen species. In recent years, PDT has been improved by the synthesis of targeted bioconjugates between monoclonal antibodies and PS, and by investigating PS biodistribution and PD. Here, we provide a comprehensive review of major developments in PS-immunoconjugate-based PDT and the bioanalysis of these agents, with a specific emphasis on anticancer and antimicrobial PDT. PMID:23641699

Recent Studies on the Care of First Febrile Urinary Tract Infection in Infants and Children for the Pediatric Hospitalist.

PubMed

Sutton, Ashley G; Chandler, Nicole; Roberts, Kenneth B

2017-01-01

Urinary Tract Infection (UTI) is a common cause of bacterial infection in young children, and accounts for a significant number of pediatric hospitalizations. To review recent publications focusing on the care of children hospitalized with their first febrile UTI. A PubMed search was performed including publications from 2011-2016 on first febrile UTI in childhood. Abstracts were reviewed for being relevant to the care of hospitalized children and their follow-up. Relevant articles underwent full review by all authors and articles excluded from results included those without novel data analysis, primary improvement-based reports and studies with poor design or analysis. Included articles were categorized as "diagnosis", "management", "imaging" or "follow-up". Of 406 articles initially identified, 40 studies were included. One technical report with a systematic review was also included. Major topics addressed included the role of urinalysis in screening for UTI, use of parenteral antimicrobial therapy, the role of antimicrobial prophylaxis in prevention of recurrent UTI, and ideal follow-up and imaging approach following diagnosis of febrile UTI. Recent literature on first febrile UTI addresses a broad range of areas regarding the care of hospitalized children, though some questions remain unanswered. Overall, studies support increased attention to the potential risks, expense and invasiveness of various approaches for evaluation. Proposed updates to practice included: utilization of urinalysis for screening and diagnosis, transitioning to oral antimicrobials based on clinical improvement and limiting the routine use of voiding cystourethrogram and antimicrobial prophylaxis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antimicrobial resistance challenged with metal-based antimicrobial macromolecules.

PubMed

Abd-El-Aziz, Alaa S; Agatemor, Christian; Etkin, Nola

2017-02-01

Antimicrobial resistance threatens the achievements of science and medicine, as it deactivates conventional antimicrobial therapeutics. Scientists respond to the threat by developing new antimicrobial platforms to prevent and treat infections from these resistant strains. Metal-based antimicrobial macromolecules are emerging as an alternative to conventional platforms because they combine multiple mechanisms of action into one platform due to the distinctive properties of metals. For example, metals interact with intracellular proteins and enzymes, and catalyse various intracellular processes. The macromolecular architecture offers a means to enhance antimicrobial activity since several antimicrobial moieties can be conjugated to the scaffold. Further, these macromolecules can be fabricated into antimicrobial materials for contact-killing medical implants, fabrics, and devices. As volatilization or leaching out of the antimicrobial moieties from the macromolecular scaffold is reduced, these medical implants, fabrics, and devices can retain their antimicrobial activity over an extended period. Recent advances demonstrate the potential of metal-based antimicrobial macromolecules as effective platforms that prevent and treat infections from resistant strains. In this review these advances are thoroughly discussed within the context of examples of metal-based antimicrobial macromolecules, their mechanisms of action and biocompatibility. Copyright © 2016 Elsevier Ltd. All rights reserved.

Staphylococcus aureus: methicillin-susceptible S. aureus to methicillin-resistant S. aureus and vancomycin-resistant S. aureus.

PubMed

Rehm, Susan J; Tice, Alan

2010-09-15

The evolution of methicillin-resistant and vancomycin-resistant Staphylococcus aureus has demanded serious review of antimicrobial use and development of new agents and revised approaches to prevent and overcome drug resistance. Depending on local conditions and patient risk factors, empirical therapy of suspected S. aureus infection may require coverage of drug-resistant organisms with newer agents and novel antibiotic combinations. The question of treatment with inappropriate antibiotics raises grave concerns with regard to methicillin-resistant S. aureus selection, overgrowth, and increased virulence. Several strategies to reduce the nosocomial burden of resistance are suggested, including shortened hospital stays and outpatient parenteral antimicrobial therapy of the most serious infections.

Prediction of distribution volume of vancomycin in critically ill patients using extravascular lung water and pulmonary vascular permeability indices.

PubMed

Imaura, Masaharu; Yokoyama, Haruko; Kohyama, Tomoki; Nagafuchi, Hiroyuki; Kohata, Yuji; Takahashi, Hiroyuki; Yamada, Yasuhiko

2012-11-01

Alterations in distribution volume affect the concentrations of hydrophilic drugs in plasma and tissues at the time of initial therapy. When the distribution volume of hydrophilic antimicrobials is increased in critically ill patients with a serious infection, antimicrobial concentrations are reduced, which may adversely affect the efficacy of antimicrobial therapy. A transpulmonary thermodilution technique system (PiCCO) enables measurements of pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), which are related to pulmonary edema and pulmonary vascular permeability, respectively. In addition, those indices may also be related to the distribution volume of hydrophilic antimicrobials. The aim of this study was to investigate the relationships of PVPI and EVLWI with the distribution volume of vancomycin (Vss), as well as to establish a method for estimating Vss for planning an appropriate initial dose for individual patients. Seven patients were administered vancomycin intravenously and underwent extended hemodynamic monitoring with the PiCCO system in the intensive care unit (ICU) from April 2009 to March 2011. Vss was calculated using the Bayesian method, and the relationships of PVPI and EVLWI with Vss were investigated. The relationship between Vss/actual body weight (ABW) and median EVLWI on days when blood levels were measured was significant (r = 0.900, p = 0.0057), whereas the relationship between Vss/ABW and PVPI was not significant (r = 0.649, p = 0.1112). EVLWI determined by the PiCCO system is useful to predict Vss and should lead to more effective vancomycin therapy for critically ill patients at the initial stage.

Long-term evaluation of the antimicrobial susceptibility and microbial profile of subgingival biofilms in individuals with aggressive periodontitis

PubMed Central

Lourenço, Talita Gomes Baêta; Heller, Débora; do Souto, Renata Martins; Silva-Senem, Mayra Xavier e; Varela, Victor Macedo; Torres, Maria Cynesia Barros; Feres-Filho, Eduardo Jorge; Colombo, Ana Paula Vieira

2015-01-01

This study evaluates the antimicrobial susceptibility and composition of subgingival biofilms in generalized aggressive periodontitis (GAP) patients treated using mechanical/antimicrobial therapies, including chlorhexidine (CHX), amoxicillin (AMX) and metronidazole (MET). GAP patients allocated to the placebo (C, n = 15) or test group (T, n = 16) received full-mouth disinfection with CHX, scaling and root planning, and systemic AMX (500 mg)/MET (250 mg) or placebos. Subgingival plaque samples were obtained at baseline, 3, 6, 9 and 12 months post-therapy from 3–4 periodontal pockets, and the samples were pooled and cultivated under anaerobic conditions. The minimum inhibitory concentrations (MICs) of AMX, MET and CHX were assessed using the microdilution method. Bacterial species present in the cultivated biofilm were identified by checkerboard DNA-DNA hybridization. At baseline, no differences in the MICs between groups were observed for the 3 antimicrobials. In the T group, significant increases in the MICs of CHX (p < 0.05) and AMX (p < 0.01) were detected during the first 3 months; however, the MIC of MET decreased at 12 months (p < 0.05). For several species, the MICs significantly changed over time in both groups, i.e., Streptococci MICs tended to increase, while for several periodontal pathogens, the MICs diminished. A transitory increase in the MIC of the subgingival biofilm to AMX and CHX was observed in GAP patients treated using enhanced mechanical therapy with topical CHX and systemic AMX/MET. Both protocols presented limited effects on the cultivable subgingival microbiota. PMID:26273264

A new rapid method for direct antimicrobial susceptibility testing of bacteria from positive blood cultures.

PubMed

Barnini, Simona; Brucculeri, Veronica; Morici, Paola; Ghelardi, Emilia; Florio, Walter; Lupetti, Antonella

2016-08-12

Rapid identification and antimicrobial susceptibility testing (AST) of the causative agent(s) of bloodstream infections can lead to prompt appropriate antimicrobial therapy. To shorten species identification, in this study bacteria were recovered from monomicrobial blood cultures by serum separator tubes and spotted onto the target plate for direct MALDI-TOF MS identification. Proper antibiotics were selected for direct AST based on species identification. In order to obtain rapid AST results, bacteria were recovered from positive blood cultures by two different protocols: by serum separator tubes (further referred to as PR1), or after a short-term subculture in liquid medium (further referred to as PR2). The results were compared with those obtained by the method currently used in our laboratory consisting in identification by MALDI-TOF and AST by Vitek 2 or Sensititre on isolated colonies. The direct MALDI-TOF method concordantly identified with the current method 97.5 % of the Gram-negative bacteria and 96.1 % of the Gram-positive cocci contained in monomicrobial blood cultures. The direct AST by PR1 and PR2 for all isolate/antimicrobial agent combinations was concordant/correct with the current method for 87.8 and 90.5 % of Gram-negative bacteria and for 93.1 and 93.8 % of Gram-positive cocci, respectively. In particular, 100 % categorical agreement was found with levofloxacin for Enterobacteriaceae by both PR1 and PR2, and 99.0 and 100 % categorical agreement was observed with linezolid for Gram-positive cocci by PR1 and PR2, respectively. There was no significant difference in accuracy between PR1 and PR2 for Gram-negative bacteria and Gram-positive cocci. This newly described method seems promising for providing accurate AST results. Most importantly, these results would be available in a few hours from blood culture positivity, which would help clinicians to promptly confirm or streamline an effective antibiotic therapy in patients with bloodstream infections.

Prostatic calculi influence the antimicrobial efficacy in men with chronic bacterial prostatitis

PubMed Central

Zhao, Wei-Ping; Li, Yong-Tao; Chen, Jun; Zhang, Zhi-Gen; Jiang, Hai; Xia, Dan; Wang, Shuo; Wang, Ping

2012-01-01

We studied the efficacy of culture-specific antibiotic therapy for chronic bacterial prostatitis (CBP) patients with or without prostatic calculi. This study included 101 patients (21–62 years old) who met the consensus criteria for CBP (National Institutes of Health category II). According to the results of transrectal ultrasonography (TRUS), all patients were divided into two groups: Group 1, CBP with prostatic calculi, n=39; Group 2, CBP without prostatic calculi, n=62. All patients received optimal antimicrobial therapy for 4 weeks and followed up for a minimum of 3 months (range: 3–8 months). In addition to expressed prostatic secretions (EPS) and urine culture, all patients were asked to complete the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the subjective global assessment (SGA). The microbiological eradication rate at the end of treatment were 32/39 (82.1%) and 54/62 (87.1%), while the rates for continued eradication at the end of study were 17/39 (43.6%) and 45/62 (72.6%) in Group 1 and Group 2 (P<0.01), respectively. We observed a decrease in the total NIH-CPSI score median values from 24 to 19 in Group 1 and from 24 to 11 in Group 2. The pain subscore (P<0.01), urinary sunscore (P<0.05) and quality of life (QoL; P<0.05) as well as the total NIH-CPSI score (P<0.01) were significantly improved after antimicrobial treatment in Group 2 compared to Group 1. Response, defined as a decrease of the NIH-CPSI total score by at least 50%, was seen in Group 1 versus Group 2 in 38.5% and 58.1% (P<0.01), respectively. Our results showed that prostatic calculi influence the antimicrobial efficacy in men with CBP. There was a noticeable decrease in the cure rate of CBP patients with prostatic calculi due to relapse after antimicrobial therapy. PMID:22796735

Prostatic calculi influence the antimicrobial efficacy in men with chronic bacterial prostatitis.

PubMed

Zhao, Wei-Ping; Li, Yong-Tao; Chen, Jun; Zhang, Zhi-Gen; Jiang, Hai; Xia, Dan; Wang, Shuo; Wang, Ping

2012-09-01

We studied the efficacy of culture-specific antibiotic therapy for chronic bacterial prostatitis (CBP) patients with or without prostatic calculi. This study included 101 patients (21-62 years old) who met the consensus criteria for CBP (National Institutes of Health category II). According to the results of transrectal ultrasonography (TRUS), all patients were divided into two groups: Group 1, CBP with prostatic calculi, n=39; Group 2, CBP without prostatic calculi, n=62. All patients received optimal antimicrobial therapy for 4 weeks and followed up for a minimum of 3 months (range: 3-8 months). In addition to expressed prostatic secretions (EPS) and urine culture, all patients were asked to complete the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the subjective global assessment (SGA). The microbiological eradication rate at the end of treatment were 32/39 (82.1%) and 54/62 (87.1%), while the rates for continued eradication at the end of study were 17/39 (43.6%) and 45/62 (72.6%) in Group 1 and Group 2 (P<0.01), respectively. We observed a decrease in the total NIH-CPSI score median values from 24 to 19 in Group 1 and from 24 to 11 in Group 2. The pain subscore (P<0.01), urinary sunscore (P<0.05) and quality of life (QoL; P<0.05) as well as the total NIH-CPSI score (P<0.01) were significantly improved after antimicrobial treatment in Group 2 compared to Group 1. Response, defined as a decrease of the NIH-CPSI total score by at least 50%, was seen in Group 1 versus Group 2 in 38.5% and 58.1% (P<0.01), respectively. Our results showed that prostatic calculi influence the antimicrobial efficacy in men with CBP. There was a noticeable decrease in the cure rate of CBP patients with prostatic calculi due to relapse after antimicrobial therapy.

Blood culture gram stain, acridine orange stain and direct sensitivity-based antimicrobial therapy of bloodstream infection in patients with trauma.

PubMed

Behera, B; Mathur, P; Gupta, B

2010-01-01

The purpose of this study was to ascertain if the simple practice of Gram stain, acridine orange stain and direct sensitivity determination of positive blood culture bottles could be used to guide early and appropriate treatment in trauma patients with clinical suspicion of sepsis. The study also aimed to evaluate the error in interpreting antimicrobial sensitivity by direct method when compared to standard method and find out if specific antibiotic-organism combination had more discrepancies. Findings from consecutive episodes of blood stream infection at an Apex Trauma centre over a 12-month period are summarized. A total of 509 consecutive positive blood cultures were subjected to Gram staining. AO staining was done in BacT/ALERT-positive Gram-stain negative blood cultures. Direct sensitivity was performed from 369 blood culture broths, showing single type of growth in Gram and acridine orange staining. Results of direct sensitivity were compared to conventional sensitivity for errors. No 'very major' discrepancy was found in this study. About 5.2 and 1.8% minor error rates were noted in gram-positive and gram-negative bacteria, respectively, while comparing the two methods. Most of the discrepancies in gram-negative bacteria were noted in beta lactam - beta lactamase inhibitor combinations. Direct sensitivity testing was not reliable for reporting of methicillin and vancomycin resistance in Staphylococci. Gram stain result together with direct sensitivity testing is required for optimizing initial antimicrobial therapy in trauma patients with clinical suspicion of sepsis. Gram staining and AO staining proved particularly helpful in the early detection of candidaemia.

Conclusions: the future of antimicrobial therapy - Augmentin and beyond.

PubMed

Ball, Peter

2007-12-01

Since most infectious microorganisms inevitably develop resistance to any agents used to combat them, there has been a constant need to produce improved, more potent, antimicrobials. At least in part, the emergence and spread of resistant organisms has been provoked by inappropriate over-use of antibacterials. In the last decade, many fewer new antibacterials have been developed but overall prescribing has continued to increase. Consensus prescribing principles have now been defined with the aim of optimising therapy and preventing further increases in, or even to prompt a reduction in, the prevalence of resistance to antibacterial agents. Whilst it is important to encourage continued development of new classes of antibacterials, it is also vital to make the best use of available agents. The development of new dosages and formulations of amoxicillin/clavulanate allows this agent to continue to fill the important role in therapy which it has occupied, and continues to occupy, 25 years after it was launched.

Host modulation therapy: An indispensable part of perioceutics

PubMed Central

Gulati, Minkle; Anand, Vishal; Govila, Vivek; Jain, Nikil

2014-01-01

Traditionally, only antimicrobials have been used as the chemotherapeutic modality for the treatment of periodontitis. Though bacteria are the primary etiologic factors of periodontal diseases, yet the extent and severity of tissue destruction seen in periodontitis is determined by the host immuno-inflammatory response to these bacteria. This increasing awareness and knowledge of the host-microbial interaction in periodontal pathogenesis has presented the opportunity for exploring new therapeutic strategies for periodontitis by means of targeting host response via host-modulating agents. This has lead to the emergence of the field of “Perioceutics” i.e. the use of parmacotherapeutic agents including antimicrobial therapy as well as host modulatory therapy for the management of periodontitis. These host-modulating agents used as an adjunct tip the balance between periodontal health and disease progression in the direction of a healing response. In this article the host-modulating role of various systemically and locally delivered perioceutic agents will be reviewed. PMID:25024538

Physical and mathematical modeling of antimicrobial photodynamic therapy

NASA Astrophysics Data System (ADS)

Bürgermeister, Lisa; López, Fernando Romero; Schulz, Wolfgang

2014-07-01

Antimicrobial photodynamic therapy (aPDT) is a promising method to treat local bacterial infections. The therapy is painless and does not cause bacterial resistances. However, there are gaps in understanding the dynamics of the processes, especially in periodontal treatment. This work describes the advances in fundamental physical and mathematical modeling of aPDT used for interpretation of experimental evidence. The result is a two-dimensional model of aPDT in a dental pocket phantom model. In this model, the propagation of laser light and the kinetics of the chemical reactions are described as coupled processes. The laser light induces the chemical processes depending on its intensity. As a consequence of the chemical processes, the local optical properties and distribution of laser light change as well as the reaction rates. The mathematical description of these coupled processes will help to develop treatment protocols and is the first step toward an inline feedback system for aPDT users.

Equine respiratory pharmacology.

PubMed

Foreman, J H

1999-12-01

Differentiation of diseases of the equine respiratory tract is based on history, clinical signs, auscultation, endoscopy, imaging, and sampling of airway exudate. Upper respiratory therapies include surgical correction of airway obstructions; flushing of localized abscesses (strangles), guttural pouch disease, or sinusitis; and oral or parenteral antibiotic and anti-inflammatory therapy if deemed necessary. Pneumonia usually is treated with antimicrobials, anti-inflammatories, and bronchodilators. Pleural drainage is indicated if significant pleural effusion is present. The most commonly used therapies for early inflammatory and chronic allergic obstructive conditions include bronchodilators and anti-inflammatories. Acute respiratory distress, particularly acute pulmonary edema, is treated with diuretics (usually furosemide), intranasal oxygen, bronchodilators, corticosteroids, and alleviation of the underlying cause. Furosemide also had been used in North America as a race-day preventative for exercise-induced pulmonary hemorrhage (EIPH), but recent data have shown that furosemide may be a performance-enhancing agent itself.

Antimicrobial resistance and prevalence of canine uropathogens at the Western College of Veterinary Medicine Veterinary Teaching Hospital, 2002–2007

PubMed Central

Ball, Katherine R.; Rubin, Joseph E.; Chirino-Trejo, M.; Dowling, Patricia M.

2008-01-01

Between January 2002 and June 2007, uropathogens were isolated from 473 of 1557 canine urine samples submitted to Prairie Diagnostic Services from the Western College of Veterinary Medicine Veterinary Teaching Hospital. Culture and susceptibility results were analyzed, retrospectively, to estimate the prevalence of common bacterial uropathogens in dogs with urinary tract infections and to identify changes in antimicrobial resistance. The most common pathogens identified were Escherichia coli, Staphylococcus intermedius, Enterococcus spp., and Proteus spp. Antimicrobial resistance increased during the study period, particularly among recurrent E. coli isolates. Using the formula to help select rational antimicrobial therapy (FRAT), bacterial isolates were most likely to be susceptible to gentamicin, fluoroquinolones, amoxicillin-clavulanic acid, and groups 4 and 5 (third generation) cephalosporins. PMID:19119366

Photo-activated porphyrin in combination with antibiotics: therapies against Staphylococci

PubMed Central

Dastgheyb, Sana S.; Eckmann, David M.; Composto, Russell J.

2013-01-01

Staphylococcal infections have become difficult to treat due to antibiotic insensitivity and resistance. Antimicrobial combination therapies may minimize acquisition of resistance and photodynamic therapy is an attractive candidate for these combinations. In this manuscript, we explore combined use of antibiotics and meso-tetra (4-aminophenyl) porphine (TAPP), a cationic porphyrin, for treatment of Staphylococcus aureus contamination. We characterize the antimicrobial activity of photoactivated TAPP and show that activity is largely lost in the presence of a radical scavenger. Importantly, TAPP can be reactivated with continued, albeit attenuated, antibacterial activity. We then show that the antimicrobial activity of illuminated TAPP is additive with chloramphenicol and tobramycin for Staphylococcus aureus and Escherichia coli, and synergistic for MRSA and Staphylococcus epidermidis. Chloramphenicol + methylene blue, another photosensitizer, also show additivity against Staphylococcus aureus. In contrast, ceftriaxone and vancomycin do not strongly augment the low level effects of TAPP against S. aureus. Eukaryotic cells exhibit a dose-dependent toxicity with illuminated TAPP. Our results suggest that even sub-minimum inhibitory concentration levels of photo-activated TAPP could be used to boost the activity of waning antibiotics. This may play an important role in treatments reliant on antibiotic controlled release systems where augmentation with photo-active agents could extend their efficacy. PMID:24148969

Successful treatment of severe Clostridium difficile infection by administration of crushed fidaxomicin via a nasogastric tube in a critically ill patient.

PubMed

Arends, Sven; Defosse, Jerome; Diaz, Cori; Wappler, Frank; Sakka, Samir G

2017-02-01

To report the successful use of crushed fidaxomicin via a nasogastric tube for treatment of a severe Clostridium difficile infection in a critically ill patient. Clinical observation of a patient, images of abdominal computed tomography, antimicrobial therapy and course of infection parameters. Relevant information contained in the medical observation of the patient and selection of image and laboratory parameters performed in the patient. We report a case of a 79-year old patient who developed septic shock with an increasing need for norepinephrine and acute renal failure due to a severe Clostridium difficile infection. Antimicrobial therapy with vancomycin via a nasogastric tube and metronidazole i.v. did not lead to improvement, infection parameters further increased, and the clinical condition became increasingly impaired. After 10 days, antimicrobial therapy was changed to fidaxomicin, crushed and administered via nasogastric tube. Within 24hours, infection parameters decreased. Further diarrhoea ceased and stool samples were negative for Clostridium difficile antigen. Our case confirms that administration of fidaxomicin via a nasogastric tube was safe and effective in this patient. Further studies are needed to evaluate the efficacy of this strategy in critically ill patients systematically. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Combination Studies of Oreganum Vulgare Extract Fractions and Volatile Oil along with Ciprofloxacin and Fluconazole against Common Fish Pathogens

PubMed Central

Bharti, Veni; Vasudeva, Neeru; Dhuhan, Joginder Singh

2013-01-01

Purpose: The study is aimed at finding new antibiotic therapy for aquaculture due to potential of bacteria to develop resistance to the existing therapies. Use of large quantities of synthetic antibiotics in aquaculture thus has the potential to be detrimental to fish health, to the environment and wildlife and to human health. Methods: Antimicrobial potential of volatile oil and fractions of chloroform extract of Oreganum vulgare was evaluated alone and in the presence of standard antimicrobials against common fish pathogens by disc-diffusion, agar well assay and two fold microdilution method by nanodrop spectrophotometric method. Results: The best results were represented by volatile oil followed by phenolic fraction by disc-diffusion, agar well and microdilution assays (Minimum inhibitory concentration). By the interaction studies, it was observed that the volatile oil and phenolic fraction were able to inhibit the pathogens at very low concentration compared to standard drugs. The fractional inhibitory concentration index (FICI) was calculated and volatile oil and phenolic fractions were found to be synergistic against Pseudomonas fluorescens and Candida albicans. Conclusion: The experimental data suggests the use of volatile oil and phenolic fraction in combination with standard antimicrobials to maintain healthy aquaculture with lesser adverse effects as compared to synthetic antibiotic therapy. PMID:24312842

Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis.

PubMed

van der Velden, Walter J F M; Herbers, Alexandra H E; Netea, Mihai G; Blijlevens, Nicole M A

2014-11-01

Infection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as 'febrile neutropenia', but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or 'mucositis'. MBI creates a port-de-entrée for resident micro-organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated host-microbe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept 'febrile neutropenia' alone may no longer suffice and a new concept 'febrile mucositis' should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host-microbe interactions arising from cytotoxic therapy-induced tissue damage in order to reduce fever in neutropenic patients with cancer. © 2014 John Wiley & Sons Ltd.

Repurposing the Nonsteroidal Anti-inflammatory Drug Diflunisal as an Osteoprotective, Antivirulence Therapy for Staphylococcus aureus Osteomyelitis.

PubMed

Hendrix, Andrew S; Spoonmore, Thomas J; Wilde, Aimee D; Putnam, Nicole E; Hammer, Neal D; Snyder, Daniel J; Guelcher, Scott A; Skaar, Eric P; Cassat, James E

2016-09-01

Staphylococcus aureus osteomyelitis is a common and debilitating invasive infection of bone. Treatment of osteomyelitis is confounded by widespread antimicrobial resistance and the propensity of bacteria to trigger pathological changes in bone remodeling that limit antimicrobial penetration to the infectious focus. Adjunctive therapies that limit pathogen-induced bone destruction could therefore limit morbidity and enhance traditional antimicrobial therapies. In this study, we evaluate the efficacy of the U.S. Food and Drug Administration-approved, nonsteroidal anti-inflammatory (NSAID) compound diflunisal in limiting S. aureus cytotoxicity toward skeletal cells and in preventing bone destruction during staphylococcal osteomyelitis. Diflunisal is known to inhibit S. aureus virulence factor production by the accessory gene regulator (agr) locus, and we have previously demonstrated that the Agr system plays a substantial role in pathological bone remodeling during staphylococcal osteomyelitis. Consistent with these observations, we find that diflunisal potently inhibits osteoblast cytotoxicity caused by S. aureus secreted toxins independently of effects on bacterial growth. Compared to commonly used NSAIDs, diflunisal is uniquely potent in the inhibition of skeletal cell death in vitro Moreover, local delivery of diflunisal by means of a drug-eluting, bioresorbable foam significantly limits bone destruction during S. aureus osteomyelitis in vivo Collectively, these data demonstrate that diflunisal potently inhibits skeletal cell death and bone destruction associated with S. aureus infection and may therefore be a useful adjunctive therapy for osteomyelitis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Inhalation Therapy in Horses.

PubMed

Cha, Mandy L; Costa, Lais R R

2017-04-01

This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

Effective Treatment of Folliculitis Decalvans Using Selected Antimicrobial Agents

PubMed Central

Sillani, Caulloo; Bin, Zhang; Ying, Zhao; Zeming, Cai; Jian, Yang; Xingqi, Zhang

2010-01-01

Folliculitis Decalvans (FD) is a rare neutrophilic infammation of the scalp characterized by painful, recurrent purulent follicular exudation resulting in primary cicatricial alopecia. However, unclear etiology makes FD treatment a difficult task. A wide variety of topical and systemic agents have been tried previously, with varied results. We present here a case series report of a set of 13 patients with FD on antimicrobial therapy. PMID:21188019

Laboratory Diagnosis of Sepsis? No SIRS, Not Just Yet

PubMed Central

2015-01-01

In order to maximize the benefit of prompt antimicrobial therapy and avoid the risk associated with inappropriate use of antimicrobial agents, patients with suspected sepsis must be rapidly differentiated from patients with systemic inflammatory response syndrome (SIRS). In combination with standard microbiological testing, a number of biomarkers have been recently evaluated for this purpose, and the performance characteristics of the most promising of these are reviewed. PMID:25631808

Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis.

PubMed

Ford, Caleb A; Cassat, James E

2017-09-01

Osteomyelitis, a common and debilitating invasive infection of bone, is a frequent complication following orthopedic surgery and causes pathologic destruction of skeletal tissues. Bone destruction during osteomyelitis results in necrotic tissue, which is poorly penetrated by antibiotics and can serve as a nidus for relapsing infection. Osteomyelitis therefore frequently necessitates surgical debridement procedures, which provide a unique opportunity for targeted delivery of antimicrobial and adjunctive therapies. Areas covered: Following surgical debridement, tissue voids require implanted materials to facilitate the healing process. Antibiotic-loaded, non-biodegradable implants have been the standard of care. However, a new generation of biodegradable, osteoconductive materials are being developed. Additionally, in the face of widespread antimicrobial resistance, alternative therapies to traditional antibiotic regimens are being investigated, including bone targeting compounds, antimicrobial surface modifications of orthopedic implants, and anti-virulence strategies. Expert commentary: Recent advances in biodegradable drug delivery scaffolds make this technology an attractive alternative to traditional techniques for orthopedic infection that require secondary operations for removal. Advances in novel treatment methods are expanding the arsenal of viable antimicrobial treatment strategies in the face of widespread drug resistance. Despite a need for large scale clinical investigations, these strategies offer hope for future treatment of this difficult invasive disease.

Advances in the Local and Targeted Delivery of Anti-infective Agents for Management of Osteomyelitis

PubMed Central

Ford, Caleb A.; Cassat, James E.

2018-01-01

Structured Abstract Introduction Osteomyelitis, a common and debilitating invasive infection of bone, is a frequent complication following orthopedic surgery and causes pathologic destruction of skeletal tissues. Bone destruction during osteomyelitis results in necrotic tissue, which is poorly penetrated by antibiotics and can serve as a nidus for relapsing infection. Osteomyelitis therefore frequently necessitates surgical debridement procedures, which provide a unique opportunity for targeted delivery of antimicrobial and adjunctive therapies. Areas Covered Following surgical debridement, tissue voids require implanted materials to facilitate the healing process. Antibiotic-loaded, non-biodegradable implants have been the standard of care. However, a new generation of biodegradable, osteoconductive materials are being developed. Additionally, in the face of widespread antimicrobial resistance, alternative therapies to traditional antibiotic regimens are being investigated, including bone targeting compounds, antimicrobial surface modifications of orthopedic implants, and anti-virulence strategies. Expert Commentary Recent advances in biodegradable drug delivery scaffolds make this technology an attractive alternative to traditional techniques for orthopedic infection that require secondary operations for removal. Advances in novel treatment methods are expanding the arsenal of viable antimicrobial treatment strategies in the face of widespread drug resistance. Despite a need for large scale clinical investigations, these strategies offer hope for future treatment of this difficult invasive disease. PMID:28837368

Comparison of treatment records and inventory of empty drug containers to quantify antimicrobial usage in dairy herds.

PubMed

Nobrega, Diego B; De Buck, Jeroen; Naqvi, S Ali; Liu, Gang; Naushad, Sohail; Saini, Vineet; Barkema, Herman W

2017-12-01

Assessment of antimicrobial use (AMU) is vital for interpreting the origin of changes in antimicrobial resistance (AMR). The objectives of the present study were to estimate the association between AMU determined using on-farm treatment records (TR) and inventory of empty drug containers (INV). Herds were selected to represent Canadian dairy farms. Producers were asked to record animal health events and treatments on a standard General Health Event form. For inventory data, 40-L receptacles were placed at various locations considered convenient to deposit all empty drug containers. Antimicrobial defined-daily dosages (ADD) were calculated for 51 Canadian herds using the 2 methods. Estimation of AMU was 31,840 ADD using the INV and 14,487 ADD using the TR, indicating that for every TR entry, 2.20 times more treatments were observed using the INV. Mastitis, reproductive conditions, and dry cow therapy were the most frequent reasons for antimicrobial therapy when assessing TR. For all antimicrobials evaluated, mean ADD was higher using the INV versus TR. Regardless, a strong positive correlation (0.80) was observed between the 2 methods, indicating that herds with increased number of ADD recorded using the INV also had increased number of ADD recorded using TR. Furthermore, a positive association was observed for the 6 most commonly used antimicrobials. In comparison to methods used in surveillance programs on AMU in livestock that assume a constant use in all herds (i.e., sales data), INV provided a herd-level specific quantity of AMU positively correlated with AMU recorded at the animal level in general. The INV was easy to implement and provided a measure of total AMU in the herd. Availability of such information would be valuable for interpreting changes in AMR at the herd level and enabling evaluation of interventions for decreasing AMR. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reduction of Broad-Spectrum Antimicrobial Use in a Tertiary Children's Hospital Post Antimicrobial Stewardship Program Guideline Implementation.

PubMed

Lee, Kelley R; Bagga, Bindiya; Arnold, Sandra R

2016-03-01

The core strategies recommended for antimicrobial stewardship programs, formulary restriction with preauthorization and prospective audit and feedback, can be difficult to implement with limited resources; therefore, we took an approach of guideline development and education with the goal of reducing overall antibiotic use and unwarranted use of broad-spectrum antimicrobials. Retrospective chart review before and after intervention. Le Bonheur Children's Hospital pediatric, neonatal, and cardiac ICUs. All patients in our pediatric, neonatal, and cardiac ICUs within the time frame of the study. Baseline review in our ICUs revealed excessive use of broad-spectrum antibiotics and inconsistency in managing common pediatric infections. Guidelines were developed and implemented using cycles of education, retrospective review, and feedback. Purchasing and antibiotic use data were obtained to assess changes before and after guideline implementation. Unit-specific days of therapy were measured using periodic chart audit. Segmented regression analysis was used to assess changes in purchasing and broad-spectrum antibiotic days of therapy. The change in median monthly purchases was assessed using 2-tail Student t test. Hospital-wide targeted broad-spectrum antibiotic days of therapy/1,000 patient-days during the preimplementation year averaged 105 per month and decreased 33% to 70 per month during the postimplementation year. The overall antibiotic days of therapy decreased 41%, 21%, and 18%, and targeted broad-spectrum antibiotic days of therapy decreased by 99%, 75%, and 61% in the cardiac, pediatric, and neonatal ICUs, respectively, after guideline implementation. Yearly purchases of our most common broad-spectrum antibiotics decreased 62% from $230,059 to $86,887 after guideline implementation. Median monthly purchases of these drugs before implementation were $19,389 and $11,043 after implementation (p < 0.001). Guideline implementation was successful in reducing targeted broad-spectrum antibiotic use and acquisition cost. Programs with very limited resources may find similar implementation of guidelines effective to provide initial success, so that putting into practice one of the more resource intensive core strategies, such as prospective audit and feedback, may be feasible.

Identifying priorities to improve paediatric in-hospital antimicrobial use by cross-sectional evaluation of prevalence and appropriateness of prescription.

PubMed

Goycochea-Valdivia, Walter Alfredo; Moreno-Ramos, Francisco; Paño-Pardo, José Ramón; Aracil-Santos, Francisco Javier; Baquero-Artigao, Fernando; Del Rosal-Rabes, Teresa; Mellado-Peña, María José; Escosa-García, Luis

2017-11-01

Information about paediatric in-hospital antimicrobial usage and prescribing patterns to guide improvement strategies is scant. We aim to use an evaluation of the prevalence and appropriateness of antimicrobial prescription to identify antimicrobial stewardship priorities in children. A cross-sectional point study was performed on hospitalised paediatric patients in a Spanish tertiary hospital, assessing the prevalence of antimicrobial prescription (PAP) and appropriateness of antimicrobial prescription (AAP). AAP was defined as a correct indication plus an appropriate prescribing pattern (dose, spectrum and interval). Evaluation was performed using established antimicrobial guidelines. Other factors that may have a bearing on antimicrobial prescription were also analysed. A total of 171 patients were included. PAP was 49.7% (85/171) and AAP was 60.9% (91/161). The most common indications for antimicrobial use were antimicrobial prophylaxis (28.3%, 32/113) and pneumonia (8.2%, 8/113). Overall, 161 antimicrobials were prescribed (1.9 antimicrobials per patient): 55.3% (89/161) were empiric, 16.1% (26/161) were targeted and 28.6% (46/161) were prophylactic. Amoxicillin/clavulanate (8.2%, 14/171) and sulfamethoxazole/trimethoprim (8.2%, 14/171) were the most prescribed antimicrobials. The prescription of antifungals (11.7%, 20/171) and antivirals (1.8%, 3/171) was analysed. Major causes of inappropriate antibiotic use were prolonged prescriptions (21.7%, 35/161) and use of agents with an excessively broad coverage spectrum (21.1%, 34/161). PAP and AAP varied between wards and antimicrobials. Measurement of PAP and AAP offers valuable information for detecting priorities in hospital settings and monitoring antimicrobial usage prior to the development of antimicrobial stewardship programmes. In our setting, the main areas for improvement are duration of therapy and proper use of broad-spectrum antimicrobials. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Costs of outpatient parenteral antimicrobial therapy (OPAT) administered by Hospital at Home units in Spain.

PubMed

González-Ramallo, V J; Mirón-Rubio, M; Mujal, A; Estrada, O; Forné, C; Aragón, B; Rivera, A J

2017-07-01

The aim of this study was to assess the direct healthcare costs of outpatient parenteral antimicrobial therapy (OPAT) administered by Hospital at Home (HaH) units in Spain. An observational, multicentre, economic evaluation of retrospective cohorts was conducted. Patients were treated at home by the HaH units of three Spanish hospitals between January 2012 and December 2013. From the cost accounting of HaH OPAT (staff, pharmacy, transportation, diagnostic tests and structural), the cost of each outpatient course was obtained following a top-down strategy based on the use of resources. Costs associated with inpatient stay, if any, were estimated based on length of stay and ICD-9-CM diagnosis. There were 1324 HaH episodes in 1190 patients (median age 70 years). The median (interquartile range) stay at home was 10 days (7-15 days). Of the OPAT episodes, 91.5% resulted in cure or improvement on completion of intravenous therapy. The mean total cost of each infectious episode was €6707 [95% confidence interval (CI) €6189-7406]. The mean cost per OPAT episode was €1356 (95% CI €1247-1560), mainly distributed between healthcare staff costs (46%) and pharmacy costs (39%). The mean cost of inpatient hospitalisation of an infectious episode was €4357 (95% CI €3947-4977). The cost per day of inpatient hospitalisation was €519, whilst the cost per day of OPAT was €98, meaning a saving of 81%. This study shows that OPAT administered by HaH units resulted in lower costs compared with inpatient care in Spain. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

The Clinical Utility of Methicillin Resistant Staphylococcus aureus (MRSA) Nasal Screening to Rule Out MRSA Pneumonia: A Diagnostic Meta-analysis with Antimicrobial Stewardship Implications.

PubMed

Parente, Diane M; Cunha, Cheston B; Mylonakis, Eleftherios; Timbrook, Tristan T

2018-01-11

Recent literature has highlighted MRSA nasal screening as a possible antimicrobial stewardship program (ASP) tool for avoiding unnecessary empiric MRSA therapy for pneumonia, yet current guidelines recommend MRSA therapy based on risk factors. The objective of this meta-analysis was to evaluate the diagnostic value of MRSA nasal screening in MRSA pneumonia. Pubmed and EMBASE were searched from inception to November 2016 for English studies evaluating MRSA nasal screening and development of MRSA pneumonia. Data analysis was performed using a bivariate random-effects model to estimate pooled sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Twenty-two studies, comprising of 5,163 patients met our inclusion criteria. Pooled sensitivity and specificity of MRSA nares screen for all MRSA pneumonia types was 70.9% and 90.3%, respectively. With a 10% prevalence of potential MRSA pneumonia, the calculated PPV was 44.8% while the NPV was 96.5%. The pooled sensitivity and specificity for MRSA community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) were at 85% and 92.1%, respectively. For CAP and HCAP both the PPV and NPV increased to 56.8% and 98.1%, respectively. In comparison, for MRSA ventilated-associated pneumonia (VAP), the sensitivity, specificity, PPV, NPV was 40.3%, 93.7%, 35.7%, and 94.8%, respectively. Nares screening for MRSA had a high specificity and NPV for ruling out MRSA pneumonia, particularly in cases of CAP/HCAP. Based on the NPV, utilization of MRSA nares screening is a valuable tool for AMS to streamline empiric antibiotic therapy, especially among patients with pneu. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Small Molecule Inhibitors of Staphylococcus aureus RnpA Alter Cellular mRNA Turnover, Exhibit Antimicrobial Activity, and Attenuate Pathogenesis

PubMed Central

Olson, Patrick D.; Kuechenmeister, Lisa J.; Anderson, Kelsi L.; Daily, Sonja; Beenken, Karen E.; Roux, Christelle M.; Reniere, Michelle L.; Lewis, Tami L.; Weiss, William J.; Pulse, Mark; Nguyen, Phung; Simecka, Jerry W.; Morrison, John M.; Sayood, Khalid; Asojo, Oluwatoyin A.; Smeltzer, Mark S.; Skaar, Eric P.; Dunman, Paul M.

2011-01-01

Methicillin-resistant Staphylococcus aureus is estimated to cause more U.S. deaths annually than HIV/AIDS. The emergence of hypervirulent and multidrug-resistant strains has further amplified public health concern and accentuated the need for new classes of antibiotics. RNA degradation is a required cellular process that could be exploited for novel antimicrobial drug development. However, such discovery efforts have been hindered because components of the Gram-positive RNA turnover machinery are incompletely defined. In the current study we found that the essential S. aureus protein, RnpA, catalyzes rRNA and mRNA digestion in vitro. Exploiting this activity, high through-put and secondary screening assays identified a small molecule inhibitor of RnpA-mediated in vitro RNA degradation. This agent was shown to limit cellular mRNA degradation and exhibited antimicrobial activity against predominant methicillin-resistant S. aureus (MRSA) lineages circulating throughout the U.S., vancomycin intermediate susceptible S. aureus (VISA), vancomycin resistant S. aureus (VRSA) and other Gram-positive bacterial pathogens with high RnpA amino acid conservation. We also found that this RnpA-inhibitor ameliorates disease in a systemic mouse infection model and has antimicrobial activity against biofilm-associated S. aureus. Taken together, these findings indicate that RnpA, either alone, as a component of the RNase P holoenzyme, and/or as a member of a more elaborate complex, may play a role in S. aureus RNA degradation and provide proof of principle for RNA catabolism-based antimicrobial therapy. PMID:21347352

Commercial Essential Oils as Potential Antimicrobials to Treat Skin Diseases

PubMed Central

Orchard, Ané

2017-01-01

Essential oils are one of the most notorious natural products used for medical purposes. Combined with their popular use in dermatology, their availability, and the development of antimicrobial resistance, commercial essential oils are often an option for therapy. At least 90 essential oils can be identified as being recommended for dermatological use, with at least 1500 combinations. This review explores the fundamental knowledge available on the antimicrobial properties against pathogens responsible for dermatological infections and compares the scientific evidence to what is recommended for use in common layman's literature. Also included is a review of combinations with other essential oils and antimicrobials. The minimum inhibitory concentration dilution method is the preferred means of determining antimicrobial activity. While dermatological skin pathogens such as Staphylococcus aureus have been well studied, other pathogens such as Streptococcus pyogenes, Propionibacterium acnes, Haemophilus influenzae, and Brevibacterium species have been sorely neglected. Combination studies incorporating oil blends, as well as interactions with conventional antimicrobials, have shown that mostly synergy is reported. Very few viral studies of relevance to the skin have been made. Encouragement is made for further research into essential oil combinations with other essential oils, antimicrobials, and carrier oils. PMID:28546822

Use of Antibiotics and Antimicrobial Resistance in Veterinary Medicine as Exemplified by the Swine Pathogen Streptococcus suis.

PubMed

Seitz, Maren; Valentin-Weigand, Peter; Willenborg, Jörg

2016-01-01

Use of antimicrobial agents in veterinary medicine is essential to control infectious diseases, thereby keeping animals healthy and animal products safe for the consumer. On the other hand, development and spread of antimicrobial resistance is of major concern for public health. Streptococcus (S.) suis reflects a typical bacterial pathogen in modern swine production due to its facultative pathogenic nature and wide spread in the pig population. Thus, in the present review we focus on certain current aspects and problems related to antimicrobial use and resistance in S. suis as a paradigm for a bacterial pathogen affecting swine husbandry worldwide. The review includes (i) general aspects of antimicrobial use and resistance in veterinary medicine with emphasis on swine, (ii) genetic resistance mechanisms of S. suis known to contribute to bacterial survival under antibiotic selection pressure, and (iii) possible other factors which may contribute to problems in antimicrobial therapy of S. suis infections, such as bacterial persister cell formation, biofilm production, and co-infections. The latter shows that we hardly understand the complexity of factors affecting the success of antimicrobial treatment of (porcine) infectious diseases and underlines the need for further research in this field.

Antimicrobial activity of sodium hypochlorite in endodontics.

PubMed

Mohammadi, Zahed; Shalavi, Sousan

2013-01-01

One of the major objectives in endodontic therapy is to disinfect the entire root canal system. This goal may be achieved using mechanical instrumenation and chemical irrigation in conjunrction with medication of the root canal between treatment sessions. Microorganisms and their by-products are considered to be the major cause of pulpal and periradicular patholic. In order to reduce or eliminate bacteria and popular tissue remnants, the use of various irrigation solution during treatment have been suggested. Sodium hypochlorite (NaOCI), the most common irrigant, is an excellent nonspecific proteolytic and antimicrobial agent. The purpose of this paper is to review the antimicrobial activity of sodium hypochlorite.

Triphenylphosphonium cation: a valuable functional group for antimicrobial photodynamic therapy.

PubMed

Bresolí-Obach, Roger; Gispert, Ignacio; García Peña, Diego; Boga, Sonia; Gulias, Óscar; Agut, Montserrat; Vázquez, M Eugenio; Nonell, Santi

2018-06-08

Light-mediated killing of pathogens by cationic photosensitisers is a promising antimicrobial approach that avoids the development of resistance inherent to the use of antimicrobials. In this study, we demonstrate that modification of different photosensitisers with the triphenylphosphonium cation yields derivatives with excellent photoantimicrobial activity against Gram-positive bacteria (i.e., S. aureus and E. faecalis). Thus, the triphenylphosphonium functional group should be considered for the development of photoantimicrobials for the selective killing of Gram-positive bacteria in the presence of Gram-negative species. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Mycobacterium marinum infection in a blue-fronted Amazon parrot (Amazona aestiva).

PubMed

Hannon, David E; Bemis, David A; Garner, Michael M

2012-12-01

A blue-fronted Amazon parrot (Amazona aestiva) was presented with a granuloma involving the proximal rhinotheca and extending into the rostral sinuses. Mycobacterium marinum was diagnosed based on results of biopsy and culture. Treatment was initiated with clarithromycin, rifampin, and ethambutol, but the bird died 4 months after the onset of antimicrobial therapy. Additional granulomas were found in the left lung and liver on postmortem examination. Mycobacterial isolation on postmortem samples was unsuccessful. This is the first report of Mycobacterium marinum in a bird.

Choosing wisely and the use of antibiotics in ophthalmic surgery: There is more than meets the eye.

PubMed

Grosso, Andrea; Ceruti, Piero; Scarpa, Giuseppe; Giardini, Franco; Marchini, Giorgio; Aragona, Emanuela; Bert, Fabrizio; Bandello, Francesco; Siliquini, Roberta

2018-02-01

One of the directions of modern ophthalmology is toward an odontoiatric model, and new settings of eye care are becoming the standard of care: one day surgery and also office-based therapies. Retrospective analysis of three tertiary-care centers in Italy and analysis of the literature. We provide readers with state-of-the-art measures of prophylaxis in ophthalmic surgery. Role of antibiotics is criticized in the light of stewardship antimicrobial paradigm.

Natural history of Mycobacterium fortuitum pulmonary infection presenting with migratory infiltrates: a case report with microbiological analysis.

PubMed

Okamori, Satoshi; Asakura, Takanori; Nishimura, Tomoyasu; Tamizu, Eiko; Ishii, Makoto; Yoshida, Mitsunori; Fukano, Hanako; Hayashi, Yuichiro; Fujita, Masaki; Hoshino, Yoshihiko; Betsuyaku, Tomoko; Hasegawa, Naoki

2018-01-02

Presence of Mycobacterium fortuitum in respiratory tracts usually indicates mere colonization or transient infection, whereas true pulmonary infection occurs in patients with gastroesophageal disease. However, little is known about the diagnostic indications for true M. fortuitum pulmonary infection and the natural history of the disease. A 59-year-old man was referred to our hospital for treatment against M. fortuitum pulmonary infection. Fifteen years before the referral, he underwent total gastrectomy, after which he experienced esophageal reflux symptoms. After the referral, the patient was closely monitored without antimicrobial therapy because of mild symptoms and no pathological evidence of M. fortuitum pulmonary infection. During the observation, chest imaging showed migratory infiltrates. Two years after the referral, his lung biopsy specimen revealed foamy macrophages and multinucleated giant cells, indicating lipoid pneumonia. However, he was continually monitored without any treatment because there was no evidence of nontuberculous mycobacterial infection. Four years after the referral, he developed refractory pneumonia despite receiving adequate antibiotic therapy. After confirmation of granulomatous lesions, multiple antimicrobial therapy for M. fortuitum resulted in a remarkable improvement with no exacerbation for over 5 years. Random amplified polymorphic DNA polymerase chain reaction analysis revealed identical M. fortuitum strains in seven isolates from six sputum and one intestinal fluid specimens obtained during the course of the disease. We have described a patient with M. fortuitum pulmonary infection who presented with migratory infiltrates. The pathological evidence and microbiological analysis suggested that M. fortuitum pulmonary infection was associated with lipoid pneumonia and chronic exposure to gastrointestinal fluid. Therefore, physicians should carefully monitor patients with M. fortuitum detected from lower respiratory tract specimens and consider antimicrobial therapy for M. fortuitum infection when the patient does not respond to adequate antibiotic therapy against common pneumonia pathogens.

Medical table: A major tool for antimicrobial stewardship policy.

PubMed

Roger, P-M; Demonchy, E; Risso, K; Courjon, J; Leroux, S; Leroux, E; Cua, É

2017-09-01

Infectious diseases are unpredictable, with heterogeneous clinical presentations, diverse pathogens, and various susceptibility rates to anti-infective agents. These features lead to a wide variety of clinical practices, which in turn strongly limits their evaluation. We have been using a medical table since 2005 to monitor the medical activity in our department. The observation of heterogeneous therapeutic practices led to drafting up our own antibiotic guidelines and to implementing a continuous evaluation of their observance and impact on morbidity and mortality associated with infectious diseases, including adverse effects of antibiotics, duration of hospital stay, use of intensive care, and deaths. The 10-year analysis of medical practices using the medical table is based on more than 10,000 hospitalizations. It shows simplified antibiotic therapies and a reduction in infection-related morbidity and mortality. The medical table is a major tool for antimicrobial stewardship, leading to constant benefits for patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Lack of efficacy of homeopathic therapy against post-calving clinical mastitis in dairy herds in the Waikato region of New Zealand.

PubMed

Williamson, J H; Lacy-Hulbert, S J

2014-01-01

To compare clinical and bacteriological cure rates of clinical mastitis following treatment with either antimicrobials or homeopathic preparations. Seven spring-calving herds from the Waikato region of New Zealand were used to source cases of clinical mastitis (n = 263 glands) during the first 90 days following calving. Duplicate milk samples were collected for bacteriology from each clinically infected gland at diagnosis and 25 (SD 5.3) days after initial treatment. Affected glands were treated with either an antimicrobial formulation or a homeopathic remedy. Generalised linear models with binomial error distribution and logit link were used to analyse the proportion of cows that were clinical treatment cures and the proportion of glands that were classified as bacteriological cures, based on initial and post-treatment milk samples. Mean cumulative incidence of clinical mastitis was 7% (range 2-13% across herds) of cows. Streptococcus uberis was the most common pathogen isolated from culture-positive samples from affected glands (140/209; 67%). The clinical cure rate was higher for cows treated with antimicrobials (107/113; 95%) than for cows treated with homeopathic remedies (72/114; 63%) (p < 0.001) based on the observance of clinical signs following initial treatment. Across all pathogen types bacteriological cure rate at gland level was higher for those cows treated with antimicrobials (75/102; 74%) than for those treated with a homeopathic preparation (39/107; 36%) (p < 0.001). Using herds located in the Waikato region of New Zealand, homeopathic remedies had significantly lower clinical and bacteriological cure rates compared with antimicrobials when used to treat post-calving clinical mastitis where S. uberis was the most common pathogen. The proportion of cows that needed retreatment was significantly higher for the homeopathic treated cows. This, combined with lower bacteriological cure rates, has implications for duration of infection, individual cow somatic cell count, costs associated with treatment and animal welfare.

Immunomodulators as adjuvants for vaccines and antimicrobial therapy.

PubMed

Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

2010-12-01

A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly.

Cross-class resistance to non-beta-lactam antimicrobials in extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.

PubMed

Procop, Gary W; Tuohy, Marion J; Wilson, Deborah A; Williams, Delisa; Hadziyannis, Emilia; Hall, Gerri S

2003-08-01

Extended spectrum beta-lactamases are modified beta-lactamase enzymes that impart resistance to third-generation cephalosporins and make all beta-lactam antibiotics and cephalosporins useless for therapy. We compared the antimicrobial susceptibility profiles of extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing isolates of Klebsiella pneumoniae. The ESBL producers had significantly diminished susceptibility compared with the non-ESBL producers for gentamicin (P < .001), tobramycin (P < .001), amikacin (P < .005), trimethoprim-sulfamethoxazole (P < .01), ciprofloxacin (P < .001), and nitrofurantoin (P < .001). All isolates were susceptible to imipenem. ESBL-producing K pneumoniae may also be resistant to non-beta-lactam antibiotics. Therefore, susceptibility testing of these isolates is critical for guiding therapy.

Photodynamic therapy as a new approach in vulvovaginal candidiasis in murine model

NASA Astrophysics Data System (ADS)

Santi, Maria E.; Lopes, Rubia G.; Prates, Renato A.; Sousa, Aline; Ferreira, Luis R.; Fernandes, Adjaci U.; Bussadori, Sandra K.; Deana, Alessandro M.

2015-02-01

Vulvovaginal candidiasis is a common cause of vaginal infections. This study investigates the efficiency of antimicrobial photodynamic therapy (aPDT) against yeast cells in mice. Methylene blue (MB), malachite green (MG), and a special designed protoporphirin (PpNetNI) were used as photosensitizers. Female BALB-c mice were infected with Candida albicans ATCC 90028. PDT was applied with two different light sources, intravaginal and transabdominal. Vaginal washes were performed and cultivated for microbial quantification. Antimicrobial PDT was able to decrease microbial content with MB and PpNetNI (p<0.05), it was not effective, however, with MG photosensitizer. The results of this study demonstrate that aPDT may be a viable alternative treatment for vaginal candidiasis.

5-Day versus 10-Day Course of Fluoroquinolones in Outpatient Males with a Urinary Tract Infection (UTI).

PubMed

Mospan, Geoffrey A; Wargo, Kurt A

Current guidelines classify urinary tract infections (UTIs) in males as complicated and recommend longer treatment than for UTIs in females. The objective of this study is to demonstrate that males with UTIs may be successfully treated with an outpatient 5-day course of levofloxacin. Data were obtained from a previously conducted clinical trial (www.clinicaltrials.gov identifier NCT00210886), a multicenter, double-blind, randomized, noninferiority study comparing levofloxacin 750 mg intravenously/by mouth once daily for 5 days and ciprofloxacin 400/500 mg intravenously/by mouth twice daily for 10 days in complicated UTI (cUTI). The current study was a post hoc, subgroup analysis of male and female subjects with cUTI. Subjects were stratified into groups based on sex and antibiotic received. The subjects were analyzed at the end of therapy (EOT) and post therapy (PT) for clinical success rates, defined as no further need for antimicrobial treatment. Totals of 427 patients (224 male, 203 female) and 350 patients (189 male, 161 female) were included in the modified intent-to-treat (mITT) population and microbiologically evaluable (ME) populations, respectively. Clinical success rates between males and females were not statistically different between antibiotic groups in either the mITT or ME populations at EOT or PT. This study demonstrates that males with UTI may be treated with a shorter course of antimicrobial therapy for UTI than previously recommended. © Copyright 2016 by the American Board of Family Medicine.

Antimicrobial photodynamic therapy in chronic osteomyelitis induced by Staphylococcus aureus: An in vitro and in vivo study

NASA Astrophysics Data System (ADS)

dos Reis Júnior, João Alves; de Assis, Patrícia Nascimento; Paraguassú, Gardênia Matos; de Vieira de Castro, Isabele Cardoso; Trindade, Renan Ferreira; Marques, Aparecida Maria Cordeiro; Almeida, Paulo Fernando; Pinheiro, Antônio Luiz Barbosa

2012-09-01

Osteomyelitis it is an acute or chronic inflammation in the marrow spaces in the superficial or cortical bone, and associated to bacterial infection. Chronic osteomyelitis represents a major health problem due to its difficult treatment and increased morbidity. Antimicrobial photodynamic therapy (APT) by laser is a treatment based on a cytotoxic photochemical reaction in which, a bright light produced by a laser system and an active photosensitizer absorbed by cells leads an activation that induces a series of metabolic reactions that culminates a bacterial killing. The aim of this study was to assess, both in vitro and in vivo, the effect of lethal laser photosensitization on osteomyelitis. On the in vitro study a diode laser (λ660nm; 40mW; o/ = 0.4 cm2; 5 or 10 J/cm2) and 5, 10 and 15μg/mL toluidine blue (TB) were tested and the best parameter chosen for the in vivo study. The concentration of 5μg/mL was selected to perform the decontamination of infected by Staphylococcus aureus tibial bone defects in rats. The results were performed by ANOVA test. On the in vitro studies all PDTs groups in the different concentrations reduced significantly (p<0,001) the amount of bacteria. On the in vivo study PDT group presented a bacterial reduction of 97,4% (P<0,001). The photodynamic therapy using toluidine blue was effective in reducing the staphiloccocus aureus in both in vitro and in vivo studies.

Risk factors for amendment in type, duration and setting of prescribed outpatient parenteral antimicrobial therapy (OPAT) for adult patients with cellulitis: a retrospective cohort study and CART analysis.

PubMed

Quirke, Michael; Curran, Emma May; O'Kelly, Patrick; Moran, Ruth; Daly, Eimear; Aylward, Seamus; McElvaney, Gerry; Wakai, Abel

2018-01-01

To measure the percentage rate and risk factors for amendment in the type, duration and setting of outpatient parenteral antimicrobial therapy ( OPAT) for the treatment of cellulitis. A retrospective cohort study of adult patients receiving OPAT for cellulitis was performed. Treatment amendment (TA) was defined as hospital admission or change in antibiotic therapy in order to achieve clinical response. Multivariable logistic regression (MVLR) and classification and regression tree (CART) analysis were performed. There were 307 patients enrolled. TA occurred in 36 patients (11.7%). Significant risk factors for TA on MVLR were increased age, increased Numerical Pain Scale Score (NPSS) and immunocompromise. The median OPAT duration was 7 days. Increased age, heart rate and C reactive protein were associated with treatment prolongation. CART analysis selected age <64.5 years, female gender and NPSS <2.5 in the final model, generating a low-sensitivity (27.8%), high-specificity (97.1%) decision tree. Increased age, NPSS and immunocompromise were associated with OPAT amendment. These identified risk factors can be used to support an evidence-based approach to patient selection for OPAT in cellulitis. The CART algorithm has good specificity but lacks sensitivity and is shown to be inferior in this study to logistic regression modelling. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Antimicrobial stewardship in a Gastroenterology Department: Impact on antimicrobial consumption, antimicrobial resistance and clinical outcome.

PubMed

Bedini, Andrea; De Maria, Nicola; Del Buono, Mariagrazia; Bianchini, Marcello; Mancini, Mauro; Binda, Cecilia; Brasacchio, Andrea; Orlando, Gabriella; Franceschini, Erica; Meschiari, Marianna; Sartini, Alessandro; Zona, Stefano; Paioli, Serena; Villa, Erica; Gyssens, Inge C; Mussini, Cristina

2016-10-01

A major cause of the increase in antimicrobial resistance is the inappropriate use of antimicrobials. To evaluate the impact on antimicrobial consumption and clinical outcome of an antimicrobial stewardship program in an Italian Gastroenterology Department. Between October 2014 and September 2015 (period B), a specialist in infectious diseases (ID) controlled all antimicrobial prescriptions and decided about the therapy in agreement with gastroenterologists. The defined daily doses of antimicrobials (DDDs), incidence of MDR-infections, mean length of stay and overall in-hospital mortality rate were compared with those of the same period in the previous 12-months (period A). During period B, the ID specialist performed 304 consultations: antimicrobials were continued in 44.4% of the cases, discontinued in 13.8%, not recommended in 12.1%, de-escalated 9.9%, escalated in 7.9%, and started in 4.0%. Comparing the 2 periods, we observed a decreased of antibiotics consumption (from 109.81 to 78.45 DDDs/100 patient-days, p=0.0005), antifungals (from 41.28 to 24.75 DDDs/100pd, p=0.0004), carbapenems (from 15.99 to 6.80 DDDsx100pd, p=0.0032), quinolones (from 35.79 to 17.82 DDDsx100pd, p=0.0079). No differences were observed in incidence of MDR-infections, length of hospital stay (LOS), and mortality rate. ASP program had a positive impact on reducing the consumption of antimicrobials, without an increase in LOS and mortality. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Can urinary nitrite results be used to conduct antimicrobial option for urinary tract infection in children?

PubMed

Mahyar, Abolfazl; Ayazi, Parviz; Froozesh, Mahta; Daneshi-Kohan, Mohammad-Mahdi; Barikani, Ameneh

2012-06-01

This study was performed to determine the relationship between urinary nitrite results and bacterial resistance to antimicrobial drugs in urinary tract infection of children. In a cross-section study 119 children younger than 12 years with urinary tract infection were evaluated in Qazvin children's hospital. Patients were divided into negative and positive nitrite groups depending on urinary nitrite test result. Rates of antibiotic resistance in the two groups were compared. Sixty seven patients were in the negative nitrite group and 52 in the positive nitrite group. Resistance rates to ceftriaxone, trimethoprim sulfamethoxazole, ampicillin, gentamicin, amikacin, nalidixic acid, cephalothin and nitrofurantoin in the nitrite negative group were 7.5%, 31.3%, 50.7%, 11.9%, 9%, 3%, 14.9% and 11.9%, respectively. These values in the nitrite positive group were 21.2%, 28.8%, 63.5%, 7.7%, 5.8%, 1.9%, 9.6%, and 3.8%, respectively (P>0.05). This study showed that there is no correlation between urinary nitrite results and bacterial resistance to antimicrobial drugs. Therefore, it seems that physicians should not adjust antibiotic therapy for UTI based on nitrite results.

Novel Polymyxin Combination With Antineoplastic Mitotane Improved the Bacterial Killing Against Polymyxin-Resistant Multidrug-Resistant Gram-Negative Pathogens.

PubMed

Tran, Thien B; Wang, Jiping; Doi, Yohei; Velkov, Tony; Bergen, Phillip J; Li, Jian

2018-01-01

Due to limited new antibiotics, polymyxins are increasingly used to treat multidrug-resistant (MDR) Gram-negative bacteria, in particular carbapenem-resistant Acinetobacter baumannii , Pseudomonas aeruginosa , and Klebsiella pneumoniae . Unfortunately, polymyxin monotherapy has led to the emergence of resistance. Polymyxin combination therapy has been demonstrated to improve bacterial killing and prevent the emergence of resistance. From a preliminary screening of an FDA drug library, we identified antineoplastic mitotane as a potential candidate for combination therapy with polymyxin B against polymyxin-resistant Gram-negative bacteria. Here, we demonstrated that the combination of polymyxin B with mitotane enhances the in vitro antimicrobial activity of polymyxin B against 10 strains of A. baumannii , P. aeruginosa , and K. pneumoniae , including polymyxin-resistant MDR clinical isolates. Time-kill studies showed that the combination of polymyxin B (2 mg/L) and mitotane (4 mg/L) provided superior bacterial killing against all strains during the first 6 h of treatment, compared to monotherapies, and prevented regrowth and emergence of polymyxin resistance in the polymyxin-susceptible isolates. Electron microscopy imaging revealed that the combination potentially affected cell division in A. baumannii . The enhanced antimicrobial activity of the combination was confirmed in a mouse burn infection model against a polymyxin-resistant A. baumannii isolate. As mitotane is hydrophobic, it was very likely that the synergistic killing of the combination resulted from that polymyxin B permeabilized the outer membrane of the Gram-negative bacteria and allowed mitotane to enter bacterial cells and exert its antimicrobial effect. These results have important implications for repositioning non-antibiotic drugs for antimicrobial purposes, which may expedite the discovery of novel therapies to combat the rapid emergence of antibiotic resistance.

Two Novel Point Mutations in Clinical Staphylococcus aureus Reduce Linezolid Susceptibility and Switch on the Stringent Response to Promote Persistent Infection

PubMed Central

Gao, Wei; Chua, Kyra; Davies, John K.; Newton, Hayley J.; Seemann, Torsten; Harrison, Paul F.; Holmes, Natasha E.; Rhee, Hyun-Woo; Hong, Jong-In; Hartland, Elizabeth L.; Stinear, Timothy P.; Howden, Benjamin P.

2010-01-01

Staphylococcus aureus frequently invades the human bloodstream, leading to life threatening bacteremia and often secondary foci of infection. Failure of antibiotic therapy to eradicate infection is frequently described; in some cases associated with altered S. aureus antimicrobial resistance or the small colony variant (SCV) phenotype. Newer antimicrobials, such as linezolid, remain the last available therapy for some patients with multi-resistant S. aureus infections. Using comparative and functional genomics we investigated the molecular determinants of resistance and SCV formation in sequential S. aureus isolates from a patient who had a persistent and recurrent S. aureus infection, after failed therapy with multiple antimicrobials, including linezolid. Two point mutations in key staphylococcal genes dramatically affected clinical behaviour of the bacterium, altering virulence and antimicrobial resistance. Most strikingly, a single nucleotide substitution in relA (SACOL1689) reduced RelA hydrolase activity and caused accumulation of the intracellular signalling molecule guanosine 3′, 5′-bis(diphosphate) (ppGpp) and permanent activation of the stringent response, which has not previously been reported in S. aureus. Using the clinical isolate and a defined mutant with an identical relA mutation, we demonstrate for the first time the impact of an active stringent response in S. aureus, which was associated with reduced growth, and attenuated virulence in the Galleria mellonella model. In addition, a mutation in rlmN (SACOL1230), encoding a ribosomal methyltransferase that methylates 23S rRNA at position A2503, caused a reduction in linezolid susceptibility. These results reinforce the exquisite adaptability of S. aureus and show how subtle molecular changes cause major alterations in bacterial behaviour, as well as highlighting potential weaknesses of current antibiotic treatment regimens. PMID:20548948

Photodynamic therapy for localized infections – state of the art

PubMed Central

Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R

2009-01-01

Photodynamic therapy (PDT) was discovered over one hundred years ago by observing the killing of microorganisms when harmless dyes and visible light were combined in vitro. Since then it has primarily been developed as a treatment for cancer, ophthalmologic disorders and in dermatology. However in recent years interest in the antimicrobial effects of PDT has revived and it has been proposed as a therapy for a large variety of localized infections. This revival of interest has largely been driven by the inexorable increase in drug resistance amongst many classes of pathogen. Advantages of PDT include equal killing effectiveness regardless of antibiotic resistance, and a lack of induction of PDT resistance. Disadvantages include the cessation of the antimicrobial effect when the light is turned off, and less than perfect selectivity for microbial cells over host tissue. This review will cover the use of PDT to kill or inactivate pathogens in ex vivo tissues and in biological materials such as blood. PDT has been successfully used to kill pathogens and even to save life in several animal models of localized infections such as surface wounds, burns, oral sites, abscesses and the middle ear. A large number of clinical studies of PDT for viral papillomatosis lesions and for acne refer to its anti-microbial effect, but it is unclear how important this microbial killing is to the overall therapeutic outcome. PDT for periodontitis is a rapidly growing clinical application and other dental applications are under investigation. PDT is being clinically studied for other dermatological infections such as leishmaniasis and mycobacteria. Antimicrobial PDT will become more important in the future as antibiotic resistance is only expected to continue to increase. PMID:19932449

Antibiotic Stewardship Initiatives as Part of the UK 5-Year Antimicrobial Resistance Strategy

PubMed Central

Johnson, Alan P.; Ashiru-Oredope, Diane; Beech, Elizabeth

2015-01-01

Antibiotic use is a major driver for the emergence and spread of antibiotic resistance. Antimicrobial stewardship programmes aim to improve antibiotic prescribing with the objectives of optimizing clinical outcomes while at the same time minimizing unintended consequences such as adverse effects and the selection of antibiotic resistance. In 2013, a five-year national strategy for tackling antimicrobial resistance was published in the UK. The overarching goal of the strategy is to slow the development and spread of resistance and to this end it has three strategic aims, namely to improve knowledge and understanding of resistance, to conserve and steward the effectiveness of existing treatments and to stimulate the development of new antibiotics, diagnostics and novel therapies. This article reviews the antimicrobial stewardship activities included in the strategy and describes their implementation and evaluation. PMID:27025636

Anthrax

DTIC Science & Technology

2009-01-01

antimicrobials listed below) Initial therapye (intravenous dosing) Oral dosing Initial therapy (intravenous) IV treatment initially Switch to oral...high index of suspicion for anthrax, initiation of therapy should not be delayed for results of these confirmatory tests. 1. MICROBIOLOGICAL TESTS...Sputum specimens from inhalational anthrax patients should be plated on chocolate agar, SBA, and MAC. Cultures will show isolated B. anthracis

75 FR 26349 - Medicare Program; Payment Policies Under the Physician Fee Schedule and Other Revisions to Part B...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-11

... (AOE): AMA-PCPI Systemic Antimicrobial Therapy-- Avoidance of Inappropriate Use. 100 Colorectal Cancer... Angiotensin Receptor Blocker (ARB) Therapy for Patients with CAD and Diabetes and/or Left Ventricular Systolic... Diabetes Mellitus. 113 Preventive Care and Screening: NCQA Colorectal Cancer Screening. TBD Hypertension...

Antimicrobial resistance in Neisseria gonorrhoeae in the UK: surveillance and management.

PubMed

Ison, Catherine A; Alexander, Sarah

2011-10-01

Successful antimicrobial therapy is fundamental to the public health control of gonorrhea, in the absence of a protective immune response. Neisseria gonorrhoeae, the causative agent, has presented a constant challenge for the provision of such therapy as it has demonstrated the ability to become resistant to successive highly active agents chosen for first-line treatment. Acquisition of plasmids from other bacteria and long-term use of a single agent has selected both single step high-level and low-level resistance due to multiple mutations. While therapeutic failure of the current recommended agents cefixime and ceftriaxone begins to emerge, choice of alternative therapies is limited. Guidelines for therapy will be dependent on surveillance programs but individual patient management will require a viable organism to detect emerging resistance. Advances in molecular detection, while advantageous for the diagnosis of gonorrhea, fail to provide a viable organism, posing even greater challenges for the definition of treatment failure, and appropriate end points for test of cure. Innovative and collaborative approaches will be essential to maintain gonorrhea as a treatable infection.

Pharmacist-driven antimicrobial stewardship in intensive care units in East China: A multicenter prospective cohort study.

PubMed

Li, Zhongwang; Cheng, Baoli; Zhang, Kai; Xie, Guohao; Wang, Yan; Hou, Jinchao; Chu, Lihua; Zhao, Jialian; Xu, Zhijun; Lu, Zhongqiu; Sun, Huaqin; Zhang, Jian; Wang, Zhiyi; Wu, Haiya; Fang, Xiangming

2017-09-01

Antimicrobial stewardship programs, particularly pharmacist-driven programs, help reduce the unnecessary use of antimicrobial agents. The objective of this study was to assess the influence of pharmacist-driven antimicrobial stewardship on antimicrobial use, multidrug resistance, and patient outcomes in adult intensive care units in China. We conducted a multicenter prospective cohort study with a sample of 577 patients. A total of 353 patients were included under a pharmacist-driven antimicrobial stewardship program, whereas the remaining 224 patients served as controls. The primary outcome was all-cause hospital mortality. The pharmacist-driven antimicrobial stewardship program had a lower hospital mortality rate compared with the nonpharmacist program (19.3% vs 29.0%; P = .007). Furthermore, logistic regression analysis indicated that the pharmacist-driven program independently predicted hospital mortality (odds ratio, 0.57; 95% confidence interval, 0.36-0.91; P = .017) after adjustment. Meanwhile, this strategy had a lower rate of multidrug resistance (23.8% vs 31.7%; P = .037). Moreover, the strategy optimized antimicrobial use, such as having a shorter duration of empirical antimicrobial therapy (2.7 days; interquartile range [IQR], 1.7-4.6 vs 3.0; IQR, 1.9-6.2; P = .002) and accumulated duration of antimicrobial treatment (4.0; IQR, 2.0-7.0 vs 5.0; IQR, 3.0-9.5; P = .030). Pharmacist-driven antimicrobial stewardship in an intensive care unit decreased patient mortality and the emergence of multidrug resistance, and optimized antimicrobial agent use. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Impact of antibiotic use in adult dairy cows on antimicrobial resistance of veterinary and human pathogens: a comprehensive review.

PubMed

Oliver, Stephen P; Murinda, Shelton E; Jayarao, Bhushan M

2011-03-01

Antibiotics have saved millions of human lives, and their use has contributed significantly to improving human and animal health and well-being. Use of antibiotics in food-producing animals has resulted in healthier, more productive animals; lower disease incidence and reduced morbidity and mortality in humans and animals; and production of abundant quantities of nutritious, high-quality, and low-cost food for human consumption. In spite of these benefits, there is considerable concern from public health, food safety, and regulatory perspectives about the use of antimicrobials in food-producing animals. Over the last two decades, development of antimicrobial resistance resulting from agricultural use of antibiotics that could impact treatment of diseases affecting the human population that require antibiotic intervention has become a significant global public health concern. In the present review, we focus on antibiotic use in lactating and nonlactating cows in U.S. dairy herds, and address four key questions: (1) Are science-based data available to demonstrate antimicrobial resistance in veterinary pathogens that cause disease in dairy cows associated with use of antibiotics in adult dairy cows? (2) Are science-based data available to demonstrate that antimicrobial resistance in veterinary pathogens that cause disease in adult dairy cows impacts pathogens that cause disease in humans? (3) Does antimicrobial resistance impact the outcome of therapy? (4) Are antibiotics used prudently in the dairy industry? On the basis of this review, we conclude that scientific evidence does not support widespread, emerging resistance among pathogens isolated from dairy cows to antibacterial drugs even though many of these antibiotics have been used in the dairy industry for treatment and prevention of disease for several decades. However, it is clear that use of antibiotics in adult dairy cows and other food-producing animals does contribute to increased antimicrobial resistance. Although antimicrobial resistance does occur, we are of the opinion that the advantages of using antibiotics in adult dairy cows far outweigh the disadvantages. Last, as this debate continues, we need to consider the consequences of "what would happen if antibiotics are banned for use in the dairy industry and in other food-producing animals?" The implications of this question are far reaching and include such aspects as animal welfare, health, and well-being, and impacts on food quantity, quality, and food costs, among others. This question should be an important aspect in this ongoing and controversial debate.

Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.

PubMed

Leone, Sebastiano; Noviello, Silvana; Esposito, Silvano

2016-06-01

Enterococci are common causes of infective endocarditis (IE) in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. For decades, cell-wall-active antimicrobial agents (penicillins or vancomycin) in combination with aminoglycosides were the cornerstone of the treatment; however, the emergence of antibiotic resistance has significantly reduced the efficacy of these regimens. Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. New effective and safe combination treatments, including double-β-lactam and daptomycin/β-lactam combination, are proving useful for the management of IE due to enterococci.

[Diagnostics and antimicrobial therapy of severe community-acquired pneumonia].

PubMed

Sinopalnikov, A I; Zaitsev, A A

2015-04-01

In the current paper authors presented the latest information concerning etiology of severe community-acquired pneumonia. Most cases are caused by a relatively small number ofpathogenic bacterial and viral natures. The frequency of detection of various pathogens of severe community-acquired pneumonia may vary greatly depending on the region, season and clinical profile of patients, availability of relevant risk factors. Authors presented clinical characteristics of severe community-acquired pneumonia and comparative evaluation of a number of scales to assess the risk of adverse outcome of the disease. Diagnosis of severe community-acquired pneumonia includes the following: collecting of epidemiological history, identification of pneumonia, detection of sepsis and identification of multiple organ dysfunction syndrome, detection of acute respiratory failure, assessment of comorbidity. Authors gave recommendations concerning evaluation of the clinical manifestations of the disease, the use of instrumental and laboratory methods for diagnosis of severe community-acquired pneumonia. To select the mode of antimicrobial therapy is most important local monitoring antimicrobial resistance of pathogens. The main criteria for the effectiveness of treatment are to reduce body temperature, severe intoxication, respiratory and organ failure.

[Obstacles and perspectives of new antimicrobial concepts within research and development].

PubMed

Kloß, Florian; Gerbach, Sina

2018-05-01

Antimicrobial resistance (AMR) has developed into a serious problem for the healthcare sector worldwide. Research on fundamentally novel antibiotics has been insufficient for decades and only a few new compounds have reached the market. Thus, the pressure to implement novel and effective concepts for the reduction of infections through problematic pathogens has dramatically increased. This demand has been recognized by politicians and comprehensive national and international funding programs have been launched. A major role of many funding lines is the investigation and development of therapeutics exerting a novel mechanism of action and/or minimizing the frequency of resistance. In addition to the actual clinical pipeline, this article lists selected examples from research and early development with a special focus on antibiotics. Moreover, alternative approaches like antivirulence and phage therapy as well as immunomodulation are summarized. AMR is no longer solely a healthcare policy, but is of societal significance as a whole. A consolidation of infrastructures and public-private partnerships, a reduction of regulatory obstacles and a continuous pursuit of innovations for antimicrobial therapy are urgently needed.

[Sharing bacterial microbiota between owners and their pets (dogs, cats)].

PubMed

Wipler, Jan; Čermáková, Zuzana; Hanzálek, Tomáš; Horáková, Hana; Žemličková, Helena

2017-06-01

The microbiological aspect of a relationship between pets (dogs/cats) and their owners is mainly concerned with the incidence of shared bacterial species, in particular potential pathogens. Given the great popularity of sharing homes with pets (dogs/cats) in the Czech Republic, there is an increased possibility of communication between microbiota of the two macroorganisms (pet and owner). The aim of the study was to determine the biodiversity of shared bacteria and possibility of exchange of genes of resistance to antimicrobial agents between potential pathogens based on the close relationship between pets and humans. A total of 103 samples were collected from 20 pairs (20 owners, 16 dogs and 4 cats). All owners completed a questionnaire with their pets' veterinarians. In owners, swabs were collected from the nasal mucosa, armpit and interdigital spaces of the foot. In pets, swabs were obtained from the external auditory meatus and nasal mucosa. In individuals with skin lesions, samples were also collected from the affected areas. Bacterial species were identified by culture and matrix-assisted laser desorption/ionization - time of flight (MALDI-TOF) mass spectrometry. In shared species, susceptibility to antibiotics was tested by the disk diffusion method. Statistical methods were used to correlate the closeness of relationship with the number of shared bacterial species and to correlate previous antimicrobial therapy with shared resistance of the common bacteria. Analysis of the questionnaires showed that 65 % of owners who participated in the study kept more pets at home than only the tested one. In the previous year, 5 % of pets and 5 % of owners received antimicrobial therapy. As many as 45 % of dogs or cats slept in their owners' beds and 80 % rested on a sofa together with their owners. Also, 45 % owners had their faces licked by pets. Eighty percent of pets were fed with several types of food (dry food and cooked food). Further, 70 % of pets lived permanently with their owners in the same household. A total of 76 bacterial species of 33 genera were identified. The most frequently isolated species (29 samples) was S. intermedius. Seventeen bacterial species occurring in both humans and animals were found and identified. At least one bacterial species was shared by 11 pairs and two shared species were found in two pairs. The shared species were S. intermedius, E. coli, E. faecalis, A. lwoffii, P. putida and S. aureus. Antimicrobial susceptibility was tested in the shared species. Common antimicrobial resistance was found in four pairs. In one pair, shared E. faecalis showed identical resistance to co-trimoxazole; in another pair, S. intermedius was resistant to gentamycin, erythromycin, clindamycin and co-trimoxazole. The third resistant bacterial species was E. coli; in one pair, it showed borderline resistance to colistin; in the second case, it was fully resistant to this antimicrobial agent. The other pairs with shared bacteria did not show any common resistance. The study results showed that there was an association between closeness of the human-pet relationship and the prevalence of shared bacterial species. Pairs with a close relationship were 37.5 % more likely to share bacteria than pairs with a less close relationship. The study suggests that antimicrobial therapy in at least one pair member may increase the risk of shared bacterial resistance.

Blue light for infectious diseases: Propionibacterium acnes, Helicobacter pylori, and beyond?

PubMed Central

Dai, Tianhong; Gupta, Asheesh; Murray, Clinton K.; Vrahas, Mark S.; Tegos, George P.; Hamblin, Michael R.

2012-01-01

Blue light, particularly in the wavelength range of 405–470 nm, has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. In addition, it is commonly accepted that blue light is much less detrimental to mammalian cells than ultraviolet irradiation, which is another light-based antimicrobial approach being investigated. In this review, we discussed the blue light sensing systems in microbial cells, antimicrobial efficacy of blue light, the mechanism of antimicrobial effect of blue light, the effects of blue light on mammalian cells, and the effects of blue light on wound healing. It has been reported that blue light can regulate multi-cellular behavior involving cell-to-cell communication via blue light receptors in bacteria, and inhibit biofilm formation and subsequently potentiate light inactivation. At higher radiant exposures, blue light exhibits a broad-spectrum antimicrobial effect against both Gram-positive and Gram-negative bacteria. Blue light therapy is a clinically accepted approach for Propionibacterium acnes infections. Clinical trials have also been conducted to investigate the use of blue light for Helicobacter pylori stomach infections and have shown promising results. Studies on blue light inactivation of important wound pathogenic bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa have also been reported. The mechanism of blue light inactivation of P. acnes, H. pylori, and some oral bacteria is the photo-excitation of intracellular porphyrins and the subsequent production of cytotoxic reactive oxygen species. Although it may be the case that the mechanism of blue light inactivation of wound pathogens (e.g., S. aureus, P. aeruginosa) is the same as that of P. acnes, this hypothesis has not been rigorously tested. Limited and discordant results have been reported regarding the effects of blue light on mammalian cells and wound healing. Under certain wavelengths and radiant exposures, blue light may cause cell dysfunction by the photo-excitation of blue light sensitive chromophores, including flavins and cytochromes, within mitochondria or/and peroxisomes. Further studies should be performed to optimize the optical parameters (e.g., wavelength, radiant exposure) to ensure effective and safe blue light therapies for infectious disease. In addition, studies are also needed to verify the lack of development of microbial resistance to blue light. PMID:22846406

The Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of H. pylori infection in adult patients in Ireland.

PubMed

Smith, Sinead; Boyle, Breida; Brennan, Denise; Buckley, Martin; Crotty, Paul; Doyle, Maeve; Farrell, Richard; Hussey, Mary; Kevans, David; Malfertheiner, Peter; Megraud, Francis; Nugent, Sean; O'Connor, Anthony; O'Morain, Colm; Weston, Shiobhan; McNamara, Deirdre

2017-05-01

Irish eradication rates for Helicobacter pylori are decreasing and there is an increase in the prevalence of antibiotic-resistant bacteria. These trends call into question current management strategies. To establish an Irish Helicobacter pylori Working Group (IHPWG) to assess, revise and tailor current available recommendations. Experts in the areas of gastroenterology and microbiology were invited to join the IHPWG. Questions of relevance to diagnosis, first-line and rescue therapy were developed using the PICO system. A literature search was performed. The 'Grading of Recommendations Assessment, Development and Evaluation' approach was then used to rate the quality of available evidence and grade the resulting recommendations. Key resultant IHPWG statements (S), the strength of recommendation and quality of evidence include S8: standard triple therapy for 7 days' duration can no longer be recommended (strong and moderate). S9: 14 days of clarithromycin-based triple therapy with a high-dose proton pump inhibitor (PPI) is recommended as first-line therapy. Bismuth quadruple therapy for 14 days is an alternative if available (strong and moderate). S12: second-line therapy depends on the first-line treatment and should not be the same treatment. The options are (a) 14 days of levofloxacin-based therapy with high-dose PPI, (b) 14 days of clarithromycin-based triple therapy with high-dose PPI or (c) bismuth quadruple therapy for 14 days (strong and moderate). S13: culture and antimicrobial susceptibility testing should be performed following two treatment failures (weak and low/very low). These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Eczema therapeutics in children: what do the clinical trials say?

PubMed

Leung, Theresa N H; Hon, K L

2015-06-01

Eczema or atopic dermatitis is a common childhood atopic disease associated with chronicity and impaired quality of life. As there is no cure for the disease, treatment relies on topical and systemic anti-allergic or immunomodulating therapies. Topical corticosteroid, macrolide immunosuppressants, and oral immunomodulating drugs for recalcitrant disease have been the mainstay of therapy. Management of atopic dermatitis must consider the individual symptomatic variability of the disease. Basic therapy is focused on patient/family education, hydrating topical treatment, and avoidance of specific and non-specific provocative factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors is used for exacerbation management and more recently in selective cases for proactive therapy. Systemic immunosuppressive treatment is an option for severe refractory cases. Microbial colonisation and superinfection may induce disease exacerbation and justify additional antimicrobial treatment. Adjuvant therapy includes ultraviolet (UV) irradiation preferably with UVA1 or narrowband UVB. Dietary recommendations should be specific and given only when food allergy is confirmed. Allergen-specific immunotherapy against aeroallergens may be useful in selected cases. Parallel use of traditional and proprietary topical and herbal medicine has also been popular in China and many cities in Asia. Complementary and alternative medicine may have a place but evidence-based data are lacking.

Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment

PubMed Central

Gjini, Erida; Brito, Patricia H.

2016-01-01

Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes. PMID:27078624

Role of biomarkers in the management of antibiotic therapy: an expert panel review: I – currently available biomarkers for clinical use in acute infections

PubMed Central

2013-01-01

In the context of worldwide increasing antimicrobial resistance, good antimicrobial prescribing in more needed than ever; unfortunately, information available to clinicians often are insufficient to rely on. Biomarkers might provide help for decision-making and improve antibiotic management. The purpose of this expert panel review was to examine currently available literature on the potential role of biomarkers to improve antimicrobial prescribing, by answering three questions: 1) Which are the biomarkers available for this purpose?; 2) What is their potential role in the initiation of antibiotic therapy?; and 3) What is their role in the decision to stop antibiotic therapy? To answer these questions, studies reviewed were limited to recent clinical studies (<15 years), involving a substantial number of patients (>50) and restricted to controlled trials and meta-analyses for answering questions 2 and 3. With regard to the first question concerning routinely available biomarkers, which might be useful for antibiotic management of acute infections, these are currently limited to C-reactive protein (CRP) and procalcitonin (PCT). Other promising biomarkers that may prove useful in the near future but need to undergo more extensive clinical testing include sTREM-1, suPAR, ProADM, and Presepsin. New approaches to biomarkers of infections include point-of-care testing and genomics. PMID:23837559

Factors associated with suitability of empiric antibiotic therapy in hospitalized patients with bloodstream infections.

PubMed

Grossman, Chagai; Keller, Nathan; Bornstein, Gil; Ben-Zvi, Ilan; Koren-Morag, Nira; Rahav, Galia

2017-06-01

Bacteremia is associated with high morbidity and mortality rates. Initiation of inadequate empiric antibiotic therapy is associated with a worse outcome. The aim of this study was to establish the prevalence and the factors associated with inappropriate empiric antibiotic therapy in patients hospitalized with bacteremia. A cross-sectional study was conducted during January 2010-December 2011 at the medical wards of the Chaim Sheba Medical Center, Israel. The records of all patients with bacteremia were reviewed. Clinical and laboratory characteristics, bacteremic pathogens and antimicrobial agents were retrieved from the medical records. Factors associated with appropriateness of empiric antibiotic therapy were assessed. A total of 681 eligible adults were included in the study. Antibiotic therapy was found to be inappropriate in 138 (20.2%) patients (95% C.I. 17.2-23.2). The rate of appropriateness was not related to the type of antibiotic regimen and the type of bacteria. Patients with healthcare-associated infections were more likely to be administrated inappropriate antibiotic therapy. Patients with primary bloodstream infections were also more likely to be administrated inappropriate antibiotic therapy. Empiric combination therapy was more likely to be appropriate than monotherapy, except for an aminoglycosides-based combination. Combination empiric antibiotic therapy should be considered in patients with healthcare-associated infections and in those with primary bloodstream infections.

One-appointment endodontic therapy: biological considerations.

PubMed

Lin, Louis M; Lin, Jarshen; Rosenberg, Paul A

2007-11-01

The authors conducted a literature review to present the best available biological evidence concerning one-appointment endodontic therapy for asymptomatic teeth with apical periodontitis. Because of recent advances in technology, such as rotary engines and nickel-titanium instruments, some practitioners are performing one-appointment endodontic therapy for asymptomatic teeth with apical periodontitis. The authors reviewed the literature, which revealed only a small number of randomized, controlled clinical trials that have been conducted on one-appointment versus multiple-appointment endodontic therapy. As the apical canal preparation is enlarged, a greater percentage of bacteria is eradicated from infected root canals. In addition, sufficiently large apical root canal enlargement facilitates the delivery of antimicrobial irrigant to the apical portion of the canal. However, an association between positive or negative preobturation root canal culture results and the outcome of endodontic treatment has not been well-established. The best available evidence, based on a systematic literature review, indicates that one-appointment endodontic therapy may be feasible in selected cases of apical periodontitis in asymptomatic teeth. However, additional randomized, controlled clinical trials are required.

Effect of the antimicrobial photodynamic therapy on microorganism reduction in deep caries lesions: a systematic review and meta-analysis.

PubMed

Ornellas, Pâmela Oliveira; Antunes, Leonardo Dos Santos; Fontes, Karla Bianca Fernandes da Costa; Póvoa, Helvécio Cardoso Corrêa; Küchler, Erika Calvano; Iorio, Natalia Lopes Pontes; Antunes, Lívia Azeredo Alves

2016-09-01

This study aimed to perform a systematic review to assess the effectiveness of antimicrobial photodynamic therapy (aPDT) in the reduction of microorganisms in deep carious lesions. An electronic search was conducted in Pubmed, Web of Science, Scopus, Lilacs, and Cochrane Library, followed by a manual search. The MeSH terms, MeSH synonyms, related terms, and free terms were used in the search. As eligibility criteria, only clinical studies were included. Initially, 227 articles were identified in the electronic search, and 152 studies remained after analysis and exclusion of the duplicated studies; 6 remained after application of the eligibility criteria; and 3 additional studies were found in the manual search. After access to the full articles, three were excluded, leaving six for evaluation by the criteria of the Cochrane Collaboration’s tool for assessing risk of bias. Of these, five had some risk of punctuated bias. All results from the selected studies showed a significant reduction of microorganisms in deep carious lesions for both primary and permanent teeth. The meta-analysis demonstrated a significant reduction in microorganism counts in all analyses (p<0.00001). Based on these findings, there is scientific evidence emphasizing the effectiveness of aPDT in reducing microorganisms in deep carious lesions.

Effect of the antimicrobial photodynamic therapy on microorganism reduction in deep caries lesions: a systematic review and meta-analysis

NASA Astrophysics Data System (ADS)

Ornellas, Pâmela Oliveira; Antunes, Leonardo Santos; Fontes, Karla Bianca Fernandes da Costa; Póvoa, Helvécio Cardoso Corrêa; Küchler, Erika Calvano; Iorio, Natalia Lopes Pontes; Antunes, Lívia Azeredo Alves

2016-09-01

This study aimed to perform a systematic review to assess the effectiveness of antimicrobial photodynamic therapy (aPDT) in the reduction of microorganisms in deep carious lesions. An electronic search was conducted in Pubmed, Web of Science, Scopus, Lilacs, and Cochrane Library, followed by a manual search. The MeSH terms, MeSH synonyms, related terms, and free terms were used in the search. As eligibility criteria, only clinical studies were included. Initially, 227 articles were identified in the electronic search, and 152 studies remained after analysis and exclusion of the duplicated studies; 6 remained after application of the eligibility criteria; and 3 additional studies were found in the manual search. After access to the full articles, three were excluded, leaving six for evaluation by the criteria of the Cochrane Collaboration's tool for assessing risk of bias. Of these, five had some risk of punctuated bias. All results from the selected studies showed a significant reduction of microorganisms in deep carious lesions for both primary and permanent teeth. The meta-analysis demonstrated a significant reduction in microorganism counts in all analyses (p<0.00001). Based on these findings, there is scientific evidence emphasizing the effectiveness of aPDT in reducing microorganisms in deep carious lesions.

Extended stability of antimicrobial agents in administration devices.

PubMed

Jenkins, Abi; Hills, Tim; Santillo, Mark; Gilchrist, Mark

2017-04-01

Outpatient parenteral antimicrobial therapy (OPAT) is an established approach to patient care. A lack of data on antimicrobial stability within administration devices is a barrier to service expansion, and poses an antimicrobial stewardship dilemma. Often broad-spectrum, long half-life agents are used instead of narrow-spectrum agents, which need more frequent administration, but could possibly be used if stability data were available. To complete a comprehensive literature review of published antimicrobial stability data, and assess these against a nationally recognized minimum dataset for medicines compounded into administration devices. Medline, EMBASE, Global Health, International Pharmaceutical Abstracts and Biomedical Research Database were interrogated in April 2014 and updated in November 2015. A total of 420 citations were reviewed with 121 selected for full text review. None of these papers met the inclusion criteria stipulated in the national standards. The most frequent reason for study exclusion was the tolerance limit for the level of the active pharmaceutical ingredient being wider than 95%-105% and absence of 'in-use' testing at 37 °C. This review found no published studies that comply with UK national standards for stability testing. We recommend further research and publication of antimicrobial stability data to support OPAT within the antimicrobial stewardship agenda. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Core groups, antimicrobial resistance and rebound in gonorrhoea in North America.

PubMed

Chan, Christina H; McCabe, Caitlin J; Fisman, David N

2012-04-01

Genital tract infections caused by Neisseria gonorrhoeae are a major cause of sexually transmitted disease worldwide. Surveillance data suggest that incidence has increased in recent years after initially falling in the face of intensified control efforts. The authors sought to evaluate the potential contribution of antimicrobial resistance to such rebound and to identify optimal treatment strategies in the face of resistance using a mathematical model of gonorrhoea. The authors built risk-structured 'susceptible-infectious-susceptible' models with and without the possibility of antibiotic resistance and used these models as a platform for the evaluation of competing plausible treatment strategies, including changing antimicrobial choice when resistance prevalence surpassed fixed thresholds, random assignment of treatment and use of combination antimicrobial therapy. Absent antimicrobial resistance, strategies that focus on treatment of highest risk individuals (the so-called core group) result in collapse of disease transmission. When antimicrobial resistance exists, a focus on the core group causes rebound in incidence, with maximal dissemination of antibiotic resistance. Random assignment of antimicrobial treatment class outperformed the use of fixed resistance thresholds with respect to sustained reduction in gonorrhoea prevalence. Gonorrhoea control is achievable only when core groups are treated, but treatment of core groups maximises dissemination of antimicrobial-resistant strains. This paradox poses a great dilemma to the control and prevention of gonorrhoea and underlines the need for gonococcal vaccines.

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

PubMed Central

Unemo, Magnus

2014-01-01

SUMMARY Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection. PMID:24982323

Old dog begging for new tricks – Current practices and future directions in the diagnosis of delayed antimicrobial hypersensitivity

PubMed Central

Konvinse, KC; Phillips, E; White, KD; Trubiano, JA

2016-01-01

Purpose of review Antimicrobials are a leading cause of severe T-cell-mediated adverse drug reactions (ADRs). The purpose of this review is to address the current understanding of antimicrobial cross-reactivity and the ready availability of and evidence for in vitro, in vivo and ex vivo diagnostics for T-cell-mediated ADRs. Recent findings Recent literature has evaluated the efficacy of traditional antibiotic allergy management including patch testing, skin prick testing, intradermal testing and oral challenge. While patch and intradermal testing are specific for the diagnosis of immune-mediated (IM) ADRs, they suffer from drug-specific limitations in sensitivity. The use of ex vivo diagnostics, especially ELISpot has been highlighted as a promising new approach to assigning causality. Knowledge of true rates of antimicrobial cross-reactivity aids empirical antibiotic choice in the setting of previous IM-ADRs. Summary In an era of increasing antimicrobial resistance and use of broad-spectrum antimicrobial therapy, ensuring patients are assigned the correct “allergy label” is essential. Re-exposure to implicated antimicrobials, especially in the setting of severe adverse cutaneous reaction is associated with significant morbidity and mortality. The process through which an antibiotic label gets assigned, acted on and maintained is still imprecise. Predicting T-cell-mediated ADRs via personalised approaches, including HLA-typing may pave future pathways to safer antimicrobial prescribing guidelines. PMID:27753687

Quinolone and Glycopeptide Therapy for Infection in Mouse Following Exposure to Mixed-Field Neutron-Gamma-Photon Radiation

DTIC Science & Technology

1993-01-01

prevents mortality, the addition of a glycopeptide can gens such as Staphylococcus spp., evaluating the enhance systemic infection by resistant...bacteria 35 10 15- 20 25 30 60 (including six E.faecalis and five Staphylococcus aureus) L IJ Days (Table 3). Treatment In the third experiment the...5.00 and 5.25Gy and most Staphylococcus spp. were of Streplococcus spp. increased. 3.3. Antimicrobial serum concentrations Antimicrobial serum

[In vitro antimicrobial, antiadherent and antifungal activity of Brazilian medicinal plants on oral biofilm microorganisms and strains of the genus Candida].

PubMed

Alves, Pollianna Muniz; Queiroz, Lélia Maria Guedes; Pereira, Jozinete Vieira; Pereira, Maria do Socorro Vieira

2009-01-01

The antimicrobial, antifungal and antiadherent activity of aroeira-do-sertão, mallow and guava tree on oral biofilm microorganisms and oral candidiasis was evaluated in vitro. The extracts were shown to be effective in inhibiting the growth of bacteria of the oral biofilm and fungi of oral candidiasis, thus suggesting that these extracts can be used as alternative means of dental therapy.

Laboratory Diagnosis of Sepsis? No SIRS, Not Just Yet.

PubMed

Dunne, W Michael

2015-08-01

In order to maximize the benefit of prompt antimicrobial therapy and avoid the risk associated with inappropriate use of antimicrobial agents, patients with suspected sepsis must be rapidly differentiated from patients with systemic inflammatory response syndrome (SIRS). In combination with standard microbiological testing, a number of biomarkers have been recently evaluated for this purpose, and the performance characteristics of the most promising of these are reviewed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Device-associated infections in the pediatric intensive care unit at the American University of Beirut Medical Center.

PubMed

Ismail, Ali; El-Hage-Sleiman, Abdul-Karim; Majdalani, Marianne; Hanna-Wakim, Rima; Kanj, Souha; Sharara-Chami, Rana

2016-06-30

Device-associated healthcare-associated infections (DA-HAIs) are the principal threat to patient safety in intensive care units (ICUs).  The primary objective of this study was to identify the most common DA-HAIs in the pediatric intensive care unit (PICU) at the American University of Beirut Medical Center (AUBMC). Length of stay (LOS) and mortality, antimicrobial resistance patterns, and suitability of empiric antibiotic choices for DA-HAIs according to the local resistance patterns were also studied. This was a retrospective study that included all patients admitted to the PICU at AUBMC between January 2007 and December 2011. All patients admitted to the PICU having a placed central line, an endotracheal tube, and/or a Foley catheter were included. Data was extracted from the patients' medical records through chart review. A total of 22 patients were identified with 25 central line-associated bloodstream infections (CLABSI), 25 ventilator-associated pneumonia (VAP), and 9 catheter-associated urinary tract infections (CAUTIs). The causing organisms, their resistance patterns, and the appropriateness of empiric antimicrobial therapy were reported. Gram-negative pathogens were found in 53% of the DA-HAIs, Gram-positive ones in 27%, and fungal organisms in 20%. A total of 80% of K. pneumonia isolates were extended-spectrum beta-lactamases (ESBL) producers, and 30% of Pseudomonas isolates were multidrug resistant. No methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) were isolated. Based on culture results, the choice of empiric antimicrobial therapy was appropriate in 64% of the DA-HAIs. After the care bundle approach is adopted in our PICU, DA-HAIs are expected to decrease further.

Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline.

PubMed

Flowers, Christopher R; Seidenfeld, Jerome; Bow, Eric J; Karten, Clare; Gleason, Charise; Hawley, Douglas K; Kuderer, Nicole M; Langston, Amelia A; Marr, Kieren A; Rolston, Kenneth V I; Ramsey, Scott D

2013-02-20

To provide guidelines on antimicrobial prophylaxis for adult neutropenic oncology outpatients and on selection and treatment as outpatients of those with fever and neutropenia. A literature search identified relevant studies published in English. Primary outcomes included: development of fever and/or infections in afebrile neutropenic outpatients and recovery without complications and overall mortality in febrile neutropenic outpatients. Secondary outcomes included: in afebrile neutropenic outpatients, infection-related mortality; in outpatients with fever and neutropenia, defervescence without regimen change, time to defervescence, infectious complications, and recurrent fever; and in both groups, hospital admissions, duration, and adverse effects of antimicrobials. An Expert Panel developed guidelines based on extracted data and informal consensus. Forty-seven articles from 43 studies met selection criteria. Antibacterial and antifungal prophylaxis are only recommended for patients expected to have < 100 neutrophils/μL for > 7 days, unless other factors increase risks for complications or mortality to similar levels. Inpatient treatment is standard to manage febrile neutropenic episodes, although carefully selected patients may be managed as outpatients after systematic assessment beginning with a validated risk index (eg, Multinational Association for Supportive Care in Cancer [MASCC] score or Talcott's rules). Patients with MASCC scores ≥ 21 or in Talcott group 4, and without other risk factors, can be managed safely as outpatients. Febrile neutropenic patients should receive initial doses of empirical antibacterial therapy within an hour of triage and should either be monitored for at least 4 hours to determine suitability for outpatient management or be admitted to the hospital. An oral fluoroquinolone plus amoxicillin/clavulanate (or plus clindamycin if penicillin allergic) is recommended as empiric therapy, unless fluoroquinolone prophylaxis was used before fever developed.

Hormonal and antimicrobial therapy in theriogenology practice: currently approved drugs in the USA and possible future directions.

PubMed

Modric, T; Momcilovic, D; Gwin, W E; Peter, A T

2011-08-01

Hormonal and antimicrobial therapies are essential to regulate and maintain healthy reproduction in domestic animals. The appropriate and legal use of these compounds is ultimately the responsibility of the veterinarian and other users, with a primary mission to directly protect and promote the health of animals, and indirectly the health of people. The appropriate use of these products is defined by the Federal Food, Drug, and Cosmetic Act, 21 United States of America § 301 et seq and implementing regulations in the Code of Federal Regulations. In the past, use of a drug in an animal for an unapproved use violated this Act. However, passage of the Animal Medicinal Drug Use Clarification Act 1994 legalized the extra-label use of certain animal and human drugs in veterinary practice for treating diseases. This manuscript reviews currently approved hormonal and antimicrobial drugs for use in theriogenology. Considering the ever increasing knowledge in the area of veterinary reproduction, particularly in the treatment and control of reproduction using antimicrobials and hormones, it would be beneficial to widen the therapeutic options in these categories. The potential for widening the therapeutic options is also discussed in this review, by providing a non-exhaustive but essential list of potential new drugs for use in clinical animal reproduction (theriogenology). Copyright © 2011 Elsevier Inc. All rights reserved.

Treatment of bacterial meningitis: an update.

PubMed

Shin, Seon Hee; Kim, Kwang Sik

2012-10-01

The introduction of protein conjugate vaccines for Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (S. pneumoniae) and Neisseria meningitidis (N. menigitidis) has changed the epidemiology of bacterial meningitis. Bacterial meningitis continues to be an important cause of mortality and morbidity, and our incomplete knowledge of its pathogenesis and emergence of antimicrobial resistant bacteria contribute to such mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis. This article gives an overview on optimal treatment strategies of bacterial meningitis, along with considerations of new insights on epidemiology, clinical and laboratory findings supportive of bacterial meningitis, chemoprophylaxis, selection of initial antimicrobial agents for suspected bacterial meningitis, antimicrobial resistance and utility of new antibiotics, status on anti-inflammatory agents and adjunctive therapy, and pathogenesis of bacterial meningitis. Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood-brain barrier (BBB), with efficacy in cerebrospinal fluid (CSF). Several new antibiotics have been introduced for the treatment of meningitis caused by resistant bacteria, but their use in human studies has been limited. More complete understanding of the microbial and host interactions that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.

Rapid antimicrobial susceptibility testing of clinical isolates by digital time-lapse microscopy.

PubMed

Fredborg, M; Rosenvinge, F S; Spillum, E; Kroghsbo, S; Wang, M; Sondergaard, T E

2015-12-01

Rapid antimicrobial susceptibility testing (AST) is essential for early and appropriate therapy. Methods with short detection time enabling same-day treatment optimisation are highly favourable. In this study, we evaluated the potential of a digital time-lapse microscope system, the oCelloScope system, to perform rapid AST. The oCelloScope system demonstrated a very high accuracy (96% overall agreement) when determining the resistance profiles of four reference strains, nine clinical isolates, including multi-drug-resistant isolates, and three positive blood cultures. AST of clinical isolates (168 antimicrobial agent-organism combinations) demonstrated 3.6% minor, no major and 1.2% very major errors of the oCelloScope system compared to conventional susceptibility testing, as well as a rapid and correct phenotypic detection of strains with methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum β-lactamase (ESBL) profiles. The net average time-to-result was 108 min, with 95% of the results being available within 180 min. In conclusion, this study strongly indicates that the oCelloScope system holds considerable potential as an accurate and sensitive AST method with short time-to-result, enabling same-day targeted antimicrobial therapy, facilitating antibiotic stewardship and better patient management. A full-scale validation of the oCelloScope system including more isolates is necessary to assess the impact of using it for AST.

Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond

PubMed Central

Vatansever, Fatma; de Melo, Wanessa C.M.A.; Avci, Pinar; Vecchio, Daniela; Sadasivam, Magesh; Gupta, Asheesh; Chandran, Rakkiyappan; Karimi, Mahdi; Parizotto, Nivaldo A; Yin, Rui; Tegos, George P; Hamblin, Michael R

2013-01-01

Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction of molecular oxygen. Four major ROS are recognized comprising: superoxide (O2•−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen (1O2), but they display very different kinetics and levels of activity. The effects of O2•− and H2O2 are less acute than those of •OH and 1O2, since the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and non-enzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or 1O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics, and non-pharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma and medicinal honey. A brief final section covers, reactive nitrogen species, and related therapeutics, such as acidified nitrite and nitric oxide releasing nanoparticles. PMID:23802986

Inappropriate use of antibiotics in hospitals: the complex relationship between antibiotic use and antimicrobial resistance.

PubMed

Cantón, Rafael; Horcajada, Juan Pablo; Oliver, Antonio; Garbajosa, Patricia Ruiz; Vila, Jordi

2013-09-01

Hospitals are considered an excellent compartment for the selection of resistant and multi-drug resistant (MDR) bacteria. The overuse and misuse of antimicrobial agents are considered key points fuelling this situation. Antimicrobial stewardship programs have been designed for better use of these compounds to prevent the emergence of resistant microorganisms and to diminish the upward trend in resistance. Nevertheless, the relationship between antibiotic use and antimicrobial resistance is complex, and the desired objectives are difficult to reach. Various factors affecting this relationship have been advocated including, among others, antibiotic exposure and mutant selection windows, antimicrobial pharmacodynamics, the nature of the resistance (natural or acquired, including mutational and that associated with horizontal gene transfer) and the definition of resistance. Moreover, antimicrobial policies to promote better use of these drugs should be implemented not only in the hospital setting coupled with infection control programs, but also in the community, which should also include animal and environmental compartments. Within hospitals, the restriction of antimicrobials, cycling and mixing strategies and the use of combination therapies have been used to avoid resistance. Nevertheless, the results have not always been favorable and resistant bacteria have persisted despite the theoretical benefits of these strategies. Mathematical models as well as microbiological knowledge can explain this failure, which is mainly related to the current scenario involving MDR bacteria and overcoming the fitness associated with resistance. New antimicrobials, rapid diagnostic and antimicrobial susceptibility testing and biomarkers will be useful for future antimicrobial stewardship interventions. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Same Day Identification and Full Panel Antimicrobial Susceptibility Testing of Bacteria from Positive Blood Culture Bottles Made Possible by a Combined Lysis-Filtration Method with MALDI-TOF VITEK Mass Spectrometry and the VITEK2 System

PubMed Central

Machen, Alexandra; Drake, Tim; Wang, Yun F. (Wayne)

2014-01-01

Rapid identification and antimicrobial susceptibility testing of microorganisms causing bloodstream infections or sepsis have the potential to improve patient care. This proof-of-principle study evaluates the Lysis-Filtration Method for identification as well as antimicrobial susceptibility testing of bacteria directly from positive blood culture bottles in a clinical setting. A total of 100 non-duplicated positive blood cultures were tested and 1012 microorganism-antimicrobial combinations were assessed. An aliquot of non-charcoal blood culture broth was incubated with lysis buffer briefly before being filtered and washed. Microorganisms recovered from the filter membrane were first identified by using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight VITEK® Mass Spectrometry (VITEK MS). After quick identification from VITEK MS, filtered microorganisms were inoculated to VITEK®2 system for full panel antimicrobial susceptibility testing analysis. Of 100 bottles tested, the VITEK MS resulted in 94.0% correct organism identification to the species level. Compared to the conventional antimicrobial susceptibility testing methods, direct antimicrobial susceptibility testing from VITEK®2 resulted in 93.5% (946/1012) category agreement of antimicrobials tested, with 3.6% (36/1012) minor error, 1.7% (7/1012) major error, and 1.3% (13/1012) very major error of antimicrobials. The average time to identification and antimicrobial susceptibility testing was 11.4 hours by using the Lysis-Filtration method for both VITEK MS and VITEK®2 compared to 56.3 hours by using conventional methods (p<0.00001). Thus, the same-day results of microorganism identification and antimicrobial susceptibility testing directly from positive blood culture can be achieved and can be used for appropriate antibiotic therapy and antibiotic stewardship. PMID:24551067

Using Informatics and the Electronic Medical Record to Describe Antimicrobial Use in the Clinical Management of Diarrhea Cases at 12 Companion Animal Practices

PubMed Central

Anholt, R. Michele; Berezowski, John; Ribble, Carl S.; Russell, Margaret L.; Stephen, Craig

2014-01-01

Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%–95.4%) and specificity (85%, 95% confidence interval, 80.2%–89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use. PMID:25057893

Antimicrobial Stewardship Programs: Appropriate Measures and Metrics to Study their Impact.

PubMed

Morris, Andrew M

Antimicrobial stewardship is a new field that struggles to find the right balance between meaningful and useful metrics to study the impact of antimicrobial stewardship programs (ASPs). ASP metrics primarily measure antimicrobial use, although microbiological resistance and clinical outcomes are also important measures of the impact an ASP has on a hospital and its patient population. Antimicrobial measures looking at consumption are the most commonly used measures, and are focused on defined daily doses, days of therapy, and costs, usually standardized per 1,000 patient-days. Each measure provides slightly different information, with their own upsides and downfalls. Point prevalence measurement of antimicrobial use is an increasingly used approach to understanding consumption that does not entirely rely on sophisticated electronic information systems, and is also replicable. Appropriateness measures hold appeal and promise, but have not been developed to the degree that makes them useful and widely applicable. The primary reason why antimicrobial stewardship is necessary is the growth of antimicrobial resistance. Accordingly, antimicrobial resistance is an important metric of the impact of an ASP. The most common approach to measuring resistance for ASP purposes is to report rates of common or important community- or nosocomial-acquired antimicrobial-resistant organisms, such as methicillin-resistant Staphylococcus aureus and Clostridium difficile. Such an approach is dependent on detection methods, community rates of resistance, and co-interventions, and therefore may not be the most accurate or reflective measure of antimicrobial stewardship interventions. Development of an index to reflect the net burden of resistance holds theoretical promise, but has yet to be realized. Finally, programs must consider patient outcome measures. Mortality is the most objective and reliable method, but has several drawbacks. Disease- or organism-specific mortality, or cure, are increasingly used metrics.

Using informatics and the electronic medical record to describe antimicrobial use in the clinical management of diarrhea cases at 12 companion animal practices.

PubMed

Anholt, R Michele; Berezowski, John; Ribble, Carl S; Russell, Margaret L; Stephen, Craig

2014-01-01

Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%-95.4%) and specificity (85%, 95% confidence interval, 80.2%-89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use.

Same day identification and full panel antimicrobial susceptibility testing of bacteria from positive blood culture bottles made possible by a combined lysis-filtration method with MALDI-TOF VITEK mass spectrometry and the VITEK2 system.

PubMed

Machen, Alexandra; Drake, Tim; Wang, Yun F Wayne

2014-01-01

Rapid identification and antimicrobial susceptibility testing of microorganisms causing bloodstream infections or sepsis have the potential to improve patient care. This proof-of-principle study evaluates the Lysis-Filtration Method for identification as well as antimicrobial susceptibility testing of bacteria directly from positive blood culture bottles in a clinical setting. A total of 100 non-duplicated positive blood cultures were tested and 1012 microorganism-antimicrobial combinations were assessed. An aliquot of non-charcoal blood culture broth was incubated with lysis buffer briefly before being filtered and washed. Microorganisms recovered from the filter membrane were first identified by using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight VITEK® Mass Spectrometry (VITEK MS). After quick identification from VITEK MS, filtered microorganisms were inoculated to VITEK®2 system for full panel antimicrobial susceptibility testing analysis. Of 100 bottles tested, the VITEK MS resulted in 94.0% correct organism identification to the species level. Compared to the conventional antimicrobial susceptibility testing methods, direct antimicrobial susceptibility testing from VITEK®2 resulted in 93.5% (946/1012) category agreement of antimicrobials tested, with 3.6% (36/1012) minor error, 1.7% (7/1012) major error, and 1.3% (13/1012) very major error of antimicrobials. The average time to identification and antimicrobial susceptibility testing was 11.4 hours by using the Lysis-Filtration method for both VITEK MS and VITEK®2 compared to 56.3 hours by using conventional methods (p<0.00001). Thus, the same-day results of microorganism identification and antimicrobial susceptibility testing directly from positive blood culture can be achieved and can be used for appropriate antibiotic therapy and antibiotic stewardship.

Tackling Threats and Future Problems of Multidrug-Resistant Bacteria.

PubMed

Medina, Eva; Pieper, Dietmar Helmut

With the advent of the antibiotic era, the overuse and inappropriate consumption and application of antibiotics have driven the rapid emergence of multidrug-resistant pathogens. Antimicrobial resistance increases the morbidity, mortality, length of hospitalization and healthcare costs. Among Gram-positive bacteria, Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) Mycobacterium tuberculosis, and among the Gram-negative bacteria, extended-spectrum beta-lactamase (ESBLs)-producing bacteria have become a major global healthcare problem in the 21st century. The pressure to use antibiotics guarantees that the spread and prevalence of these as well as of future emerging multidrug-resistant pathogens will be a persistent phenomenon. The unfeasibility of reversing antimicrobial resistance back towards susceptibility and the critical need to treat bacterial infection in modern medicine have burdened researchers and pharmaceutical companies to develop new antimicrobials effective against these difficult-to-treat multidrug-resistant pathogens. However, it can be anticipated that antibiotic resistance will continue to develop more rapidly than new agents to treat these infections become available and a better understanding of the molecular, evolutionary and ecological mechanisms governing the spread of antibiotic resistance is needed. The only way to curb the current crisis of antimicrobial resistance will be to develop entirely novel strategies to fight these pathogens such as combining antimicrobial drugs with other agents that counteract and obstruct the antibiotic resistant mechanisms expressed by the pathogen. Furthermore, as many antibiotics are often inappropriately prescribed, a more personalized approach based on precise diagnosis tools will ensure that proper treatments can be promptly applied leading to more targeted and effective therapies. However, in more general terms, also the overall use and release of antibiotics in the environment needs to be better controlled.

Impact of computerized pre-authorization of broad spectrum antibiotics in Pseudomonas aeruginosa at a children's hospital in Japan.

PubMed

Horikoshi, Yuho; Higuchi, Hiroshi; Suwa, Junichi; Isogai, Mihoko; Shoji, Takayo; Ito, Kenta

2016-08-01

The spread of antimicrobial-resistant organisms is a global concern. To stem this tide, an antimicrobial stewardship program at hospitals is essential to optimize the prescription of broad spectrum antibiotics. In this study we examined the impact of computerized pre-authorization for broad spectrum antibiotics for Pseudomonas aeruginosa at a children's hospital. An antimicrobial stewardship program at Tokyo Metropolitan Children's Medical Center was assessed between March 2010 and March 2015. A paper-based post-prescription audit was switched to computerized pre-authorization for broad antipseudomonal agents in October 2011. The prescriber was required to obtain approval from physicians in the pediatric infectious diseases division before prescribing restricted antimicrobial agents. Approved prescriptions were processed and logged electronically. We evaluated days of therapy per 1000 patient-days, the cost of antibiotics, and the susceptibility of P. aeruginosa to piperacillin, ceftazidime, cefepime, piperacillin/tazobactam, carbapenems, and ciprofloxacin. Also, the average length of admission and infection-related mortality at 30 days were compared pre- and post-intervention. Administration of carbapenems, piperacillin/tazobactam, and ceftazidime decreased significantly after the introduction of computerized pre-authorization. Antibiotic costs were reduced by JPY2.86 million (USD 26,000) annually. None of the antipseudomonal agents showed decreased sensitivity. The average length of admission was shorter in post-intervention. Infection-related mortality at 30 days showed no difference between the pre- and post-intervention periods. An antimicrobial stewardship program using computerized pre-authorization decreased the use and cost of broad spectrum antibiotics without significant difference in infection-related mortality at 30 days, although our study did not improve susceptibilities of P. aeruginosa. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Efficacy of early switch from intravenous to oral antimicrobials in patients with aspiration pneumonia: A prospective observational study.

PubMed

Uni, Masahiro; Nishimura, Naoki; Yamano, Yasuhiko; Ishikawa, Genta; Kitamura, Atsushi; Tomishima, Yutaka; Jinta, Torahiko; Takahashi, Osamu; Deshpande, Gautam; Chohnabayashi, Naohiko

2015-09-01

Previous reports have documented the efficacy of an early switch from intravenous to oral antimicrobials in community-acquired pneumonia, but not aspiration pneumonia. Therefore, we assessed the feasibility and efficacy of these newly developed criteria for community-acquired pneumonia in patients with aspiration pneumonia. This prospective observational study included consecutive patients admitted with aspiration pneumonia over a 10-month period at St. Luke's International Hospital; we excluded patients that required intensive care. The criteria for an early switch were stability of vital signs (temperature ≤ 38 °C; respiratory rate ≤ 24 breaths/min; pulse rate ≤ 100 beats/min for >24 h) and a successful swallow evaluation (repetitive saliva swallowing test score ≥ 2; modified water swallowing test score ≥ 4). Our primary endpoint was successful completion of antimicrobial treatment 30 days after the switch, without reversion to intravenous antimicrobials. Our anticipated success rate was set as 60-75%, based on a previous study. Of the 70 patients admitted with aspiration pneumonia, 32 (45.7%) were excluded, and 38 (54.3%) met the inclusion criteria. Of these 38 patients, 29 (76.3%) met the switch criteria. The median duration of hospital stay for the included patients was 16 (5-30) days and 30 (12-68) days, respectively (P=0.03). Among patients who met the switch criteria, 26 (89.7%) completed oral treatment successfully while 3 (10.3%) reverted to intravenous antimicrobials. Approximately 75% of patients met the switch criteria; of these, nearly 90% underwent safe conversion to oral therapy. These results demonstrate the efficacy and feasibility of our switch criteria. Copyright © 2015. Published by Elsevier B.V.

Local drug delivery agents as adjuncts to endodontic and periodontal therapy

PubMed Central

Puri, K; Puri, N

2013-01-01

Abstract In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained/controlled drug release, high antimicrobial activity and low systemic side effects. The conventional method for the elimination of subgingival microbial infection includes mechanical debridement, irrigation with antimicrobial agents or surgical access. But, the effectiveness of conventional nonsurgical treatment is limited by lack of accessibility to bacteria in deeper periodontal pockets, and/or does not completely eliminate intracanal microorganisms. Surgical intervention may be beneficial but cannot be done in all cases, medically compromised cases and also in patients not willing to be subjected to surgical therapy. Development of local drug delivery systems provides an answer to all such difficulties. This comprehensive review tries to cover the detailed information about the latest advances in the various local drug delivery systems, their indications, contraindications and their advantages over systemic drug therapy. PMID:24868252

Urinary tract infection.

PubMed

Nicolle, Lindsay E

2013-07-01

The urinary tract is a common source for life-threatening infections. Most patients with sepsis or septic shock from a urinary source have complicated urinary tract infection. This article explains the epidemiology, risk factors, and treatment. Effective management, appropriate collection of microbiology specimens, prompt initiation of antimicrobial therapy, source control, and supportive therapy are described. Copyright © 2013 Elsevier Inc. All rights reserved.

Cost-effectiveness of ceftolozane/tazobactam plus metronidazole compared with piperacillin/tazobactam as empiric therapy for the treatment of complicated intra-abdominal infections based on the in-vitro surveillance of bacterial isolates in the UK.

PubMed

Prabhu, Vimalanand; Foo, Jason; Ahir, Harblas; Sarpong, Eric; Merchant, Sanjay

2017-08-01

An increase in the prevalence of antimicrobial resistance among gram-negative pathogens has been noted recently. A challenge in empiric treatment of complicated intra-abdominal infection (cIAI) is identifying initial appropriate antibiotic therapy, which is associated with reduced length of stay and mortality compared with inappropriate therapy. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam + metronidazole compared with piperacillin/tazobactam (commonly used in this indication) in the treatment of patients with cIAI in UK hospitals. A decision-analytic Monte Carlo simulation model was used to compare costs (antibiotic and hospitalization costs) and quality-adjusted life years (QALYs) of patients infected with gram-negative cIAI and treated empirically with either ceftolozane/tazobactam + metronidazole or piperacillin/tazobactam. Bacterial isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients in the UK infected with gram-negative pathogens. Susceptibility to initial empiric therapy was based on the measured susceptibilities reported in the PACTS database. Ceftolozane/tazobactam + metronidazole was cost-effective when compared with piperacillin/tazobactam, with an incremental cost-effectiveness ratio (ICER) of £4,350/QALY and 0.36 hospitalization days/patient saved. Costs in the ceftolozane/tazobactam + metronidazole arm were £2,576/patient, compared with £2,168/patient in the piperacillin/tazobactam arm. The ceftolozane/tazobactam + metronidazole arm experienced a greater number of QALYs than the piperacillin/tazobactam arm (14.31/patient vs 14.21/patient, respectively). Ceftolozane/tazobactam + metronidazole remained cost-effective in one-way sensitivity and probabilistic sensitivity analyses. Economic models can help to identify the appropriate choice of empiric therapy for the treatment of cIAI. Results indicated that empiric use of ceftolozane/tazobactam + metronidazole is cost-effective vs piperacillin/tazobactam in UK patients with cIAI at risk of resistant infection. This will be valuable to commissioners and clinicians to aid decision-making on the targeting of resources for appropriate antibiotic therapy under the premise of antimicrobial stewardship.

[Apitherapy--the role of honey in the chronic wound healing process].

PubMed

Majtán, J

2009-08-01

With increasing frequency, modern medicine directs attention to natural products and biological therapy methods and their use in clinical practice. Bee honey as well as other bee products (propolis, royal jelly and venom) have already found use in medicine not only as immune system stimulants but also as chronic wound healing promoters. The major arguments for implementing apitherapy are the low cost in comparison with conventional therapies and the fact that honey has proved effective against resistant hospital pathogens. Besides antimicrobial characteristics associated with no antimicrobial resistance risk, honey has anti-inflammatory effects. Controlled clinical trials have shown honey to be effective in chronic wound healing and gave rise to medihoney. Nevertheless, further study is needed to confirm the efficacy and safety of honey in clinical practice.

Application of Nanoparticle Technologies in the Combat against Anti-Microbial Resistance.

PubMed

Kumar, Mayur; Curtis, Anthony; Hoskins, Clare

2018-01-14

Anti-microbial resistance is a growing problem that has impacted the world and brought about the beginning of the end for the old generation of antibiotics. Increasingly, more antibiotics are being prescribed unnecessarily and this reckless practice has resulted in increased resistance towards these drugs, rendering them useless against infection. Nanotechnology presents a potential answer to anti-microbial resistance, which could stimulate innovation and create a new generation of antibiotic treatments for future medicines. Preserving existing antibiotic activity through novel formulation into or onto nanotechnologies can increase clinical longevity of action against infection. Additionally, the unique physiochemical properties of nanoparticles can provide new anti-bacterial modes of action which can also be explored. Simply concentrating on antibiotic prescribing habits will not resolve the issue but rather mitigate it. Thus, new scientific approaches through the development of novel antibiotics and formulations is required in order to employ a new generation of therapies to combat anti-microbial resistance.

Antimicrobial Effect of Jasminum grandiflorum L. and Hibiscus rosa-sinensis L. Extracts Against Pathogenic Oral Microorganisms--An In Vitro Comparative Study.

PubMed

Nagarajappa, Ramesh; Batra, Mehak; Sharda, Archana J; Asawa, Kailash; Sanadhya, Sudhanshu; Daryani, Hemasha; Ramesh, Gayathri

2015-01-01

To assess and compare the antimicrobial potential and determine the minimum inhibitory concentration (MIC) of Jasminum grandiflorum and Hibiscus rosa-sinensis extracts as potential anti-pathogenic agents in dental caries. Aqueous and ethanol (cold and hot) extracts prepared from leaves of Jasminum grandiflorum and Hibiscus rosa-sinensis were screened for in vitro antimicrobial activity against Streptococcus mutans and Lactobacillus acidophilus using the agar well diffusion method. The lowest concentration of every extract considered as the minimum inhibitory concentration (MIC) was determined for both test organisms. Statistical analysis was performed with one-way analysis of variance (ANOVA). At lower concentrations, hot ethanol Jasminum grandiflorum (10 μg/ml) and Hibiscus rosa-sinensis (25 μg/ml) extracts were found to have statistically significant (P≤0.05) antimicrobial activity against S. mutans and L. acidophilus with MIC values of 6.25 μg/ml and 25 μg/ml, respectively. A proportional increase in their antimicrobial activity (zone of inhibition) was observed. Both extracts were found to be antimicrobially active and contain compounds with therapeutic potential. Nevertheless, clinical trials on the effect of these plants are essential before advocating large-scale therapy.

An overview of antimicrobial peptides and the latest advances in their development.

PubMed

Sierra, Josep M; Fusté, Ester; Rabanal, Francesc; Vinuesa, Teresa; Viñas, Miguel

2017-06-01

The recent dramatic increase in the incidence of antimicrobial resistance has been recognized by organizations such as the United Nations and World Health Organization as well as the governments of the USA and several European countries. A relatively new weapon in the fight against severe infections caused by multi-drug resistant bacteria is antimicrobial peptides (AMPs). These include colistin, currently regarded as the last line of antimicrobial therapy against multi-drug resistant microorganisms. Areas covered: Here, the authors provide an overview of the current research on AMPs. The focus is AMPs currently being developed for the treatment of recalcitrant bacterial infections, the synergies of AMPs and antibiotics, and the activity of AMPs against biofilm. This review also includes a brief introduction into the use of AMPs in infections caused by Mycobacterium, fungi, and parasites. Expert opinion: In research into new antimicrobials, AMPs are gaining increasing attention. While many are natural and are produced by a wide variety of organisms, others are being newly designed and chemically synthesized in the laboratory to achieve novel antimicrobial agents. The same strategy to fight infections in nature is thus being effectively exploited to safeguard human and animal health.

Pharmacokinetic-pharmacodynamic (PK-PD) modeling and the rational selection of dosage regimes for the prudent use of antimicrobial drugs.

PubMed

Papich, Mark G

2014-07-16

One of the strategies to decrease inappropriate antimicrobial use in veterinary medicine is to apply pharmacokinetic-pharmacodynamic (PK-PD) principles to dosing regimens. If antimicrobials are used appropriately by applying these principles to attain targets for area-under-the-curve to MIC ratio (AUC/MIC), peak concentration to MIC ratio (CMAX/MIC), and time above MIC (T>MIC), more effective antibiotic therapy is possible, thus avoiding ineffective administration. Another mechanism whereby inappropriate antibiotic administration can be avoided is to use accurate Interpretive Criteria established by the Clinical Laboratory Standards Institute (CLSI) for breakpoint selection. Inaccurate breakpoints will encourage antibiotic administration that is likely to be ineffective. For newly approved antimicrobials, three criteria are used for determining breakpoints: PK-PD criteria, MIC distributions, and clinical response. For older (often generic drugs) evaluated by the CLSI, recent clinical data may not be available and breakpoints are derived from PK-PD principles, wild-type distributions, and Monte Carlo simulations. It is the goal of the CLSI subcommittee that these revised breakpoints will encourage more effective antimicrobial use and avoid unnecessary antimicrobial administration. Copyright © 2014 Elsevier B.V. All rights reserved.

Isolation, molecular characterization and antimicrobial susceptibilities of isolates of Mycoplasma agalactiae from bulk tank milk in an endemic area of Spain.

PubMed

de Garnica, M L; Rosales, R S; Gonzalo, C; Santos, J A; Nicholas, R A J

2013-06-01

To isolate and characterize strains of Mycoplasma agalactiae from bulk tank and silo ewes' milk. Thirteen mycoplasma isolates were obtained from samples of sheep milk taken from bulk tank and large silos and identified as Myc. agalactiae by PCR-DGGE. The isolates were typed by pulsed field gel electrophoresis (PFGE), SDS-PAGE and immunoblot. The in vitro activity of 13 antimicrobials of veterinary interest was tested against these isolates. Results showed that the most effective compounds against Myc. agalactiae in vitro were clindamycin, an antibiotic not previously described as a suitable contagious agalactia (CA) treatment, with Minimum Inhibitory Concentration (MIC) values of <0·12 μg ml(-1) , and quinolones, with MIC values <0·12-0·5 μg ml(-1) , which are used as standard treatments against CA. Based on the in vitro assay, clindamycin, quinolones, tylosin and tilmicosin would be appropriate antimicrobials for CA treatment. The isolates were mostly resistant to erythromycin, indicating that it would not be a suitable choice for therapy. The isolates showed common molecular and protein profiles by PFGE and SDS-PAGE, with minor differences observed by immunoblot analysis, suggesting a clonal relationship among them. This study demonstrated the importance of the appropriate selection of antimicrobials for treatment of CA. © [2013] Crown copyright. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

Treatment of Helicobacter pylori infection: Current status and future concepts

PubMed Central

Yang, Jyh-Chin; Lu, Chien-Wei; Lin, Chun-Jung

2014-01-01

Helicobacter pylori (H. pylori) infection is highly associated with the occurrence of gastrointestinal diseases, including gastric inflammation, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid-tissue lymphoma. Although alternative therapies, including phytomedicines and probiotics, have been used to improve eradication, current treatment still relies on a combination of antimicrobial agents, such as amoxicillin, clarithromycin, metronidazole, and levofloxacin, and antisecretory agents, such as proton pump inhibitors (PPIs). A standard triple therapy consisting of a PPI and two antibiotics (clarithromycin and amoxicillin/metronidazole) is widely used as the first-line regimen for treatment of infection, but the increased resistance of H. pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy. Alternatively, levofloxacin-based triple therapy can be used as rescue therapy for H. pylori infection after failure of first-line therapy. The increase in resistance to antibiotics, including levofloxacin, may limit the applicability of such regimens. However, since resistance of H. pylori to amoxicillin is generally low, an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy. In addition, the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H. pylori infection, though its efficacy needs to be verified in clinical studies. PMID:24833858

Antimicrobial therapy of experimental Legionella micdadei pneumonia in guinea pigs.

PubMed Central

Pasculle, A W; Dowling, J N; Frola, F N; McDevitt, D A; Levi, M A

1985-01-01

Several antimicrobial agents were evaluated for activity against experimental Legionella micdadei pneumonia in guinea pigs. Erythromycin, rifampin, doxycycline, and sulfamethoxazole-trimethoprim produced significant reductions in mortality. Penicillin, cefazolin, cefoxitin, chloramphenicol, and gentamicin were not efficacious even though, at the doses administered, the peak concentrations of these agents in serum substantially exceeded their MICs for the test strain. It is suggested that the poor performance of the latter group of agents resulted from poor penetration into cells in which L. micdadei was multiplying. PMID:3878688

Next-Generation Probiotics Targeting Clostridium difficile through Precursor-Directed Antimicrobial Biosynthesis

PubMed Central

Auchtung, Jennifer; Brown, Aaron; Boonma, Prapaporn; Oezguen, Numan; Ross, Caná L.; Luna, Ruth Ann; Runge, Jessica; Versalovic, James; Peniche, Alex; Dann, Sara M.; Britton, Robert A.; Haag, Anthony; Savidge, Tor C.

2017-01-01

ABSTRACT Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials. PMID:28760934

Encapsulation of curcumin in polymeric nanoparticles for antimicrobial Photodynamic Therapy

PubMed Central

Trigo Gutierrez, Jeffersson Krishan; Zanatta, Gabriela Cristina; Ortega, Ana Laura Mira; Balastegui, Maria Isabella Cuba; Sanitá, Paula Volpato; Pavarina, Ana Cláudia; Barbugli, Paula Aboud

2017-01-01

Curcumin (CUR) has been used as photosensitizer in antimicrobial Photodynamic Therapy (aPDT). However its poor water solubility, instability, and scarce bioavalibility hinder its in vivo application. The aim of this study was to synthesize curcumin in polymeric nanoparticles (NP) and to evaluate their antimicrobial photodynamic effect and cytoxicity. CUR in anionic and cationic NP was synthesized using polylactic acid and dextran sulfate by the nanoprecipitation method. For cationic NP, cetyltrimethylammonium bromide was added. CUR-NP were characterized by physicochemical properties, photodegradation, encapsulation efficiency and release of curcumin from nanoparticles. CUR-NP was compared with free CUR in 10% dimethyl sulfoxide (DMSO) as a photosensitizer for aPDT against planktonic and biofilms (mono-, dual- and triple-species) cultures of Streptococcus mutans, Candida albicans and Methicillin-Resistant Staphylococcus aureus. The cytotoxicity effect of formulations was evaluated on keratinocytes. Data were analysed by parametric (ANOVA) and non-parametric (Kruskal-Wallis) tests (α = 0.05). CUR-NP showed alteration in the physicochemical properties along time, photodegradation similar to free curcumin, encapsulation efficiency up to 67%, and 96% of release after 48h. After aPDT planktonic cultures showed reductions from 0.78 log10 to complete eradication, while biofilms showed no antimicrobial effect or reductions up to 4.44 log10. Anionic CUR-NP showed reduced photoinactivation of biofilms. Cationic CUR-NP showed microbicidal effect even in absence of light. Anionic formulations showed no cytotoxic effect compared with free CUR and cationic CUR-NP and NP. The synthesized formulations improved the water solubility of CUR, showed higher antimicrobial photodynamic effect for planktonic cultures than for biofilms, and the encapsulation of CUR in anionic NP reduced the cytotoxicity of 10% DMSO used for free CUR. PMID:29107978

Indocyanine green (ICG) as a new adjuvant for the antimicrobial photo-dynamic therapy (aPDT) in dentistry

NASA Astrophysics Data System (ADS)

Meister, Joerg; Hopp, Michael; Schäfers, Johannes; Verbeek, Jonas; Kraus, Dominik; Frentzen, Matthias

2014-02-01

Clinical surveys show a continuous increase of antimicrobial resistance related to the frequency of the administrated medication. The antimicrobial photodynamic therapy (aPDT) is an effective adjuvant to reduce the need of antibiotics in dentistry, especially in periodontics. The antimicrobial effect of lightactivated photosensitizers in periodontics is demonstrated in clinical studies and case reports. Indocyanine green (ICG) as a new adjuvant shows the high potential of antiphlogistic and antimicrobial effects in combination with laser-light activation. In trying to answer the question of just how far the influence of temperature is acting on bacteria, this study was carried out. The influences of ICG at different concentrations (0.01 up to 1 mg/ml) in combination with a culture medium (brain-heart-infusion) and a bacteria culture (Streptococcus salivarius) at different optical densities (OD600 0.5 and 0.1) were investigated under laser-light activation. Laser activation was carried out with diode laser at 810 nm and two different power settings (100 mW/300 mW). The pulse repetition rate was 2 kHz. Taking account of the fiber diameter, distance and spot size on the sample surface, the applicated intensities were 6.2 and 18.7 W/cm2. Total irradiation time was 20 s for all meaurements. Transmitted laser power and temperature increase in the culture medium as well as in the bacteria culture were determined. Additionally the influence of ICG regarding bacterial growth and bactericidal effect was investigated in the bacteria culture without laser irradiation. Without laser, no bactericidal effect of ICG was observed. Only a bacteriostatic effect could be proved. In dependence of the ICG concentration and the applied intensities a temperature increase of ΔT up to 80°C was measured.

Quantitative Assessment of Combination Antimicrobial Therapy against Multidrug-Resistant Acinetobacter baumannii▿

PubMed Central

Lim, Tze-Peng; Ledesma, Kimberly R.; Chang, Kai-Tai; Hou, Jing-Guo; Kwa, Andrea L.; Nikolaou, Michael; Quinn, John P.; Prince, Randall A.; Tam, Vincent H.

2008-01-01

Treatment of multidrug-resistant bacterial infections poses a therapeutic challenge to clinicians; combination therapy is often the only viable option for multidrug-resistant infections. A quantitative method was developed to assess the combined killing abilities of antimicrobial agents. Time-kill studies (TKS) were performed using a multidrug-resistant clinical isolate of Acinetobacter baumannii with escalating concentrations of cefepime (0 to 512 mg/liter), amikacin (0 to 256 mg/liter), and levofloxacin (0 to 64 mg/liter). The bacterial burden data in single and combined (two of the three agents with clinically achievable concentrations in serum) TKS at 24 h were mathematically modeled to provide an objective basis for comparing various antimicrobial agent combinations. Synergy and antagonism were defined as interaction indices of <1 and >1, respectively. A hollow-fiber infection model (HFIM) simulating various clinical (fluctuating concentrations over time) dosing exposures was used to selectively validate our quantitative assessment of the combined killing effect. Model fits in all single-agent TKS were satisfactory (r2 > 0.97). An enhanced combined overall killing effect was seen in the cefepime-amikacin combination (interactive index, 0.698; 95% confidence interval [CI], 0.675 to 0.722) and the cefepime-levofloxacin combination (interactive index, 0.929; 95% CI, 0.903 to 0.956), but no significant difference in the combined overall killing effect for the levofloxacin-amikacin combination was observed (interactive index, 0.994; 95% CI, 0.982 to 1.005). These assessments were consistent with observations in HFIM validation studies. Our method could be used to objectively rank the combined killing activities of two antimicrobial agents when used together against a multidrug-resistant A. baumannii isolate. It may offer better insights into the effectiveness of various antimicrobial combinations and warrants further investigations. PMID:18505848

Supervised learning for infection risk inference using pathology data.

PubMed

Hernandez, Bernard; Herrero, Pau; Rawson, Timothy Miles; Moore, Luke S P; Evans, Benjamin; Toumazou, Christofer; Holmes, Alison H; Georgiou, Pantelis

2017-12-08

Antimicrobial Resistance is threatening our ability to treat common infectious diseases and overuse of antimicrobials to treat human infections in hospitals is accelerating this process. Clinical Decision Support Systems (CDSSs) have been proven to enhance quality of care by promoting change in prescription practices through antimicrobial selection advice. However, bypassing an initial assessment to determine the existence of an underlying disease that justifies the need of antimicrobial therapy might lead to indiscriminate and often unnecessary prescriptions. From pathology laboratory tests, six biochemical markers were selected and combined with microbiology outcomes from susceptibility tests to create a unique dataset with over one and a half million daily profiles to perform infection risk inference. Outliers were discarded using the inter-quartile range rule and several sampling techniques were studied to tackle the class imbalance problem. The first phase selects the most effective and robust model during training using ten-fold stratified cross-validation. The second phase evaluates the final model after isotonic calibration in scenarios with missing inputs and imbalanced class distributions. More than 50% of infected profiles have daily requested laboratory tests for the six biochemical markers with very promising infection inference results: area under the receiver operating characteristic curve (0.80-0.83), sensitivity (0.64-0.75) and specificity (0.92-0.97). Standardization consistently outperforms normalization and sensitivity is enhanced by using the SMOTE sampling technique. Furthermore, models operated without noticeable loss in performance if at least four biomarkers were available. The selected biomarkers comprise enough information to perform infection risk inference with a high degree of confidence even in the presence of incomplete and imbalanced data. Since they are commonly available in hospitals, Clinical Decision Support Systems could benefit from these findings to assist clinicians in deciding whether or not to initiate antimicrobial therapy to improve prescription practices.

Urinary Tract Infection: Pathogenesis and Outlook

PubMed Central

McLellan, Lisa K.; Hunstad, David A.

2016-01-01

The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. PMID:27692880

Treatments of clinical mastitis occurring in cows on 51 large dairy herds in Wisconsin.

PubMed

Oliveira, L; Ruegg, P L

2014-09-01

Antimicrobials are frequently used for treatment of bovine mastitis and few studies have examined modern treatment strategies on large US dairy farms. The objective of this study was to describe treatment practices for clinical mastitis occurring in cows on large dairy herds in Wisconsin. Treatments performed on 747 cows experiencing cases of mild, moderate, or severe symptoms of clinical mastitis were recorded on 51 Wisconsin dairy farms. Duplicate milk samples were collected from the affected quarter for microbiological analysis at the onset of clinical mastitis and 14 to 21 d after treatment ended. Cows were treated according to individual farm protocol. Drugs and doses used for treatments were recorded for each case. Among all herds, 5 intramammary (IMM) antimicrobials (amoxicillin, hetacillin, pirlimycin, ceftiofur, and cephapirin) were used to treat cows for clinical mastitis. Of 712 cows with complete treatment data, 71.6% were treated with IMM ceftiofur either solely or combined with other antimicrobials (administered either IMM or systemically). Of cows experiencing severe symptoms of clinical mastitis, 43.8% received IMM treatment concurrent with systemic antimicrobials. Of all cows treated, 23.1% received an additional secondary treatment (either IMM, systemic, or both) because of perceived lack of response to the initial treatment. The majority of IMM treatments were administered to cows with a microbiological diagnosis of no growth (34.9%) or Escherichia coli (27.2%). Half of the cows experiencing cases caused by E. coli were treated using systemic antimicrobials in contrast to only 6.8% of cows experiencing cases caused by coagulase-negative staphylococci. In conflict with FDA regulations, which do not allow extra-label treatments using sulfonamides, a total of 22 cows from 8 farms were treated with systemic sulfadimethoxine either solely or in combination with oxytetracycline. Antimicrobial drugs were used on all herds and many cows received extra-label treatments. Great opportunity exists to improve mastitis therapy on large dairy herds, but use of more diagnostic methodologies is necessary to guide treatments. Farmers and veterinarians should work together to create protocols based on the herd needs considering reduced inappropriate and excessive use of antimicrobials. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effect of active packaging incorporated with triclosan on bacteria adhesion.

PubMed

Camilloto, Geany P; Pires, Ana Clarissa S; Soares, Nilda de Fátima F; Araújo, Emiliane A; Andrade, Nélio J; Ferreira, Sukarno O

2010-10-01

Antimicrobial polyethylene and cellulose based films incorporated with triclosan were studied. The antimicrobial efficacy, the hydrophobicity, microscopic and the mechanical characteristics of the films, as well free energy of adhesion between bacteria and antimicrobial films were evaluated. It was observed that both polyethylene and cellulose based films incorporated with the antimicrobial were homogeneous. Furthermore, the addition of triclosan did not affect mechanical characteristics of the films (P > 0.05). However, triclosan incorporated into polyethylene films reduced its hydrophobicity while antimicrobial cellulose based films became more hydrophobic. The adhesion was thermodynamically favorable between tested bacteria and polyethylene films. On the other hand, the adhesion to triclosan cellulose based film was thermodynamically unfavorable to Staphylococcus aureus and Escherichia coli and favorable to Listeria innocua and Pseudomonas aeruginosa. Polyethylene and cellulose based films showed inhibitory effect against S. aureus and E. coli, being the inhibition halo higher for polyethylene films. This study improves the knowledge about antimicrobial films.

Microfluidic-Based Bacteria Isolation from Whole Blood for Diagnostics of Blood Stream Infection.

PubMed

Zelenin, Sergey; Ramachandraiah, Harisha; Faridi, Asim; Russom, Aman

2017-01-01

Bacterial blood stream infection (BSI) potentially leads to life-threatening clinical conditions and medical emergencies such as severe sepsis, septic shock, and multi organ failure syndrome. Blood culturing is currently the gold standard for the identification of microorganisms and, although it has been automated over the decade, the process still requires 24-72 h to complete. This long turnaround time, especially for the identification of antimicrobial resistance, is driving the development of rapid molecular diagnostic methods. Rapid detection of microbial pathogens in blood related to bloodstream infections will allow the clinician to decide on or adjust the antimicrobial therapy potentially reducing the morbidity, mortality, and economic burden associated with BSI. For molecular-based methods, there is a lot to gain from an improved and straightforward method for isolation of bacteria from whole blood for downstream processing.We describe a microfluidic-based sample-preparation approach that rapidly and selectively lyses all blood cells while it extracts intact bacteria for downstream analysis. Whole blood is exposed to a mild detergent, which lyses most blood cells, and then to osmotic shock using deionized water, which eliminates the remaining white blood cells. The recovered bacteria are 100 % viable, which opens up possibilities for performing drug susceptibility tests and for nucleic-acid-based molecular identification.

Development and evaluation of thymol-chitosan hydrogels with antimicrobial-antioxidant activity for oral local delivery.

PubMed

Alvarez Echazú, María Inés; Olivetti, Christian Ezequiel; Anesini, Claudia; Perez, Claudio Javier; Alvarez, Gisela Solange; Desimone, Martin Federico

2017-12-01

Nowadays, the research of innovative drug delivery devices is focused on the design of multiple drug delivery systems, the prevention of drug side effects and the reduction of dosing intervals. Particularly, new mucosal delivery systems for antimicrobials, antioxidants and anti-inflammatory drugs has a growing development, regards to the avoidance of side effects, easy administration and a suitable drug concentration in the mucosa. In this work, chitosan hydrogels are evaluated as a biodegradable scaffold and as a bioactive agent carrier of an antioxidant-antimicrobial compound called thymol. Throughout the study, swelling behavior, viscoelastic properties and thermal analysis are highlighted to present its advantages for a biomedical application. Furthermore, the in vitro results obtained indicate that thymol-chitosan hydrogels are biocompatible when exposed to [3T3] fibroblasts, exhibit antimicrobial activity against Staphylococcus aureus and Streptococcus mutans for 72h and antioxidant activity for 24h. These are desirable properties for a mucosal delivery system for an antimicrobial-antioxidant dual therapy for periodontal disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Point-of-Prescription Interventions to Improve Antimicrobial Stewardship

PubMed Central

Hamilton, Keith W.; Gerber, Jeffrey S.; Moehring, Rebekah; Anderson, Deverick J.; Calderwood, Michael S.; Han, Jennifer H.; Mehta, Jimish M.; Pollack, Lori A.; Zaoutis, Theoklis; Srinivasan, Arjun; Camins, Bernard C.; Schwartz, David N.; Lautenbach, Ebbing

2015-01-01

Antimicrobial stewardship is pivotal to improving patient outcomes, reducing adverse events, decreasing healthcare costs, and preventing further emergence of antimicrobial resistance. In an era in which antimicrobial resistance is increasing, judicious antimicrobial use is the responsibility of every healthcare provider. Antimicrobial stewardship programs (ASPs) have made headway in improving antimicrobial prescribing using such “top-down” methods as formulary restriction and prospective audit with feedback; however, engagement of prescribers has not been fully explored. Strategies that include frontline prescribers and other unit-based healthcare providers have the potential to expand stewardship, both to augment existing centralized ASPs and to provide alternative approaches to perform stewardship at healthcare facilities with limited resources. This review discusses interventions focusing on antimicrobial prescribing at the point of prescription as well as a pilot project to engage unit-based healthcare providers in antimicrobial stewardship. PMID:25595748

Maintenance after a complex orthoperio treatment in a case of generalized aggressive periodontitis: 7-year result.

PubMed

Zafiropoulos, Gregory-George; di Prisco, Manuela Occipite; Deli, Giorgio; Hoffmann, Oliver; Kasaj, Adrian

2010-10-01

Generalized aggressive periodontitis (GAgP) encompasses a distinct type of periodontal disease exhibiting much more rapid periodontal tissue destruction than chronic periodontitis. The best method for management of GAgP may include the use of both regenerative periodontal techniques and the administration of systemic antibiotics. The treatment of a case of GAgP over a period of 6.7 years is presented in this case report. Initial periodontal therapy (week 1- 32) consisted of supragingival plaque control and three appointments of scaling and root planing. Based on the periodontal pathogens isolated (5 species), the patient also received metronidazole plus amoxicillin for one week, followed 10 weeks later by metronidazole plus amoxicillin/clavulanate for one week. The patient was put on regular supportive periodontal therapy (SPT) thereafter. Orthodontic treatment was performed after completion of the initial therapy for 96 weeks. Measurements of clinical attachment level, bleeding on probing and plaque index were obtained at every examination. Antimicrobial and mechanical treatment resulted in eradication of all periopathogens and significantly improved all clinical parameters. During orthodontic treatment and active maintenance, there was no relapse of GAgP. The patient participated in SPT for 194 weeks and thereafter decided to discontinue SPT. Twenty-four months later a relapse of GAgP was diagnosed and all teeth had to be extracted. These results indicate that a combined mechanical and antimicrobial treatment approach can lead to consistent resolution of GAgP. Further studies including a larger number of cases are warranted to validate these findings.

Hyperosmolar metabolic acidosis in burn patients exposed to glycol based topical antimicrobials-A systematic review.

PubMed

Leibson, Tom; Davies, Paige; Nickel, Cheri; Koren, Gideon

2018-06-01

The well documented susceptibility of burn patients to acquired infections via damaged skin mandates application of antimicrobial agents. These agents are dissolved in various vehicles that augment skin absorption thus allowing greater efficacy. Polyethylene glycol (PEG) and Propylene glycol (PropG) are among the most commonly used vehicles, and both have been used in numerous medications and cosmetic products over the past few decades. Rarely, burn patients treated with agents containing these glycols present with a life threatening systemic toxidrome of hyperosmolar metabolic acidosis. We present a systematic review of outcomes in burn patients treated with similar agents. Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters), from database inception to August 4th, 2016. All publications of clinical burn patient studies included at least one arm receiving a glycol based topical therapy. A total of 61 studies involving 10,282 patients and 4 different antimicrobial medications fulfilled the inclusion criteria. Nine burn patients (0.09%) were documented to present with hyperosmolar metabolic acidosis during topical silver sulfadiazine treatment. Propylene glycol isolated from their blood accounted for the high osmole gap. This first systematic review found very few cases of documented hyperosmolar metabolic acidosis, all within one study that had set to specifically explore this toxidrome. High index of suspicion with frequent osmolar gap monitoring may help identify future toxicities in a timely manner. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Antimicrobial susceptibility survey on bacterial agents of canine and feline urinary tract infections: Weight of the empirical treatment.

PubMed

Rampacci, Elisa; Bottinelli, Marco; Stefanetti, Valentina; Hyatt, Doreene R; Sgariglia, Elisa; Coletti, Mauro; Passamonti, Fabrizio

2018-06-01

This work characterised the antimicrobial susceptibility of uropathogens isolated from empirically treated dogs and cats. Within-household transmission of uropathogens can involve humans and companion animals. Knowledge on the prevalence and susceptibility pattern of isolates from canine and feline urine samples and the impact of prior antimicrobial treatment is important to prevent the dissemination of antimicrobial resistance. A retrospective study was conducted selecting antibiotic-treated companion animals. Urine samples were collected by cystocentesis and were submitted to an Italian diagnostic laboratory over a 2-year period (2013-2015). The antimicrobial susceptibility of the isolates was analysed both using Clinical and Laboratory Standards Institute (CLSI) guidelines and a formula to help select rational antimicrobial therapy. Gram-negative bacteria were clearly prevalent. Gentamicin had the highest impact factors. Amoxicillin/clavulanic acid and doxycycline appeared to be the most effective compounds against Gram-positive infections, whilst marbofloxacin may be a useful option against Gram-negative urinary tract infections (UTIs) as well as doxycycline and trimethoprim/sulfamethoxazole in cats and dogs, respectively. Consulting published studies, a comparable overall trend regarding bacterial species incriminated in canine and feline UTIs and their susceptibilities seems likely, despite different circumstances where the studies were conducted. Companion animals are potential reservoirs of drug-resistant uropathogens. Judicious use of antibiotics is necessary to maintain the efficacy of antimicrobials in human and veterinary medicine. Antimicrobial susceptibility monitoring programmes are therefore essential to facilitate the choice of antimicrobial agent that is most likely to be effective, particularly in cases of prior antimicrobial treatment. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. All rights reserved.

Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes.

PubMed

Costa, Patrícia de Oliveira; Atta, Elias Hallack; Silva, André Ricardo Araújo da

2015-01-01

This study aimed at evaluating the predictors and outcomes associated with multidrug-resistant gram-negative bacterial (MDR-GNB) infections in an oncology pediatric intensive care unit (PICU). Data were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR-GNB and (2) infections attributed to non-MDR-GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare-associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7- and 30-day mortality. Multivariate logistic regression analyses showed significant relationships between MDR-GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282-21.594; p=0.021) and healthcare-associated infection (OR 18.360; 95% CI 1.778-189.560; p=0.015). There were significant differences between MDR-GNB and non-MDR-GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. Hematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

A World Wide Web-based antimicrobial stewardship program improves efficiency, communication, and user satisfaction and reduces cost in a tertiary care pediatric medical center.

PubMed

Agwu, Allison L; Lee, Carlton K K; Jain, Sanjay K; Murray, Kara L; Topolski, Jason; Miller, Robert E; Townsend, Timothy; Lehmann, Christoph U

2008-09-15

Antimicrobial stewardship programs aim to reduce inappropriate hospital antimicrobial use. At the Johns Hopkins Children's Medical and Surgical Center (Baltimore, MD), we implemented a World Wide Web-based antimicrobial restriction program to address problems with the existing restriction program. A user survey identified opportunities for improvement of an existing antimicrobial restriction program and resulted in subsequent design, implementation, and evaluation of a World Wide Web-based antimicrobial restriction program at a 175-bed, tertiary care pediatric teaching hospital. The program provided automated clinical decision support, facilitated approval, and enhanced real-time communication among prescribers, pharmacists, and pediatric infectious diseases fellows. Approval status, duration, and rationale; missing request notifications; and expiring approvals were stored in a database that is accessible via a secure Intranet site. Before and after implementation of the program, user satisfaction, reports of missed and/or delayed doses, antimicrobial dispensing times, and cost were evaluated. After implementation of the program, there was a $370,069 reduction in projected annual cost associated with restricted antimicrobial use and an 11.6% reduction in the number of dispensed doses. User satisfaction increased from 22% to 68% and from 13% to 69% among prescribers and pharmacists, respectively. There were 21% and 32% reductions in the number of prescriber reports of missed and delayed doses, respectively, and there was a 37% reduction in the number of pharmacist reports of delayed approvals; measured dispensing times were unchanged (P = .24). In addition, 40% fewer restricted antimicrobial-related phone calls were noted by the pharmacy. The World Wide Web-based antimicrobial approval program led to improved communication, more-efficient antimicrobial administration, increased user satisfaction, and significant cost savings. Integrated tools, such as this World Wide Web-based antimicrobial approval program, will effectively enhance antimicrobial stewardship programs.

Infectious Disease Management through Point-of-Care Personalized Medicine Molecular Diagnostic Technologies

PubMed Central

Bissonnette, Luc; Bergeron, Michel G.

2012-01-01

Infectious disease management essentially consists in identifying the microbial cause(s) of an infection, initiating if necessary antimicrobial therapy against microbes, and controlling host reactions to infection. In clinical microbiology, the turnaround time of the diagnostic cycle (>24 hours) often leads to unnecessary suffering and deaths; approaches to relieve this burden include rapid diagnostic procedures and more efficient transmission or interpretation of molecular microbiology results. Although rapid nucleic acid-based diagnostic testing has demonstrated that it can impact on the transmission of hospital-acquired infections, we believe that such life-saving procedures should be performed closer to the patient, in dedicated 24/7 laboratories of healthcare institutions, or ideally at point of care. While personalized medicine generally aims at interrogating the genomic information of a patient, drug metabolism polymorphisms, for example, to guide drug choice and dosage, personalized medicine concepts are applicable in infectious diseases for the (rapid) identification of a disease-causing microbe and determination of its antimicrobial resistance profile, to guide an appropriate antimicrobial treatment for the proper management of the patient. The implementation of point-of-care testing for infectious diseases will require acceptance by medical authorities, new technological and communication platforms, as well as reimbursement practices such that time- and life-saving procedures become available to the largest number of patients. PMID:25562799

Management of Acute Diarrhoea in Primary Care in Bahrain: Self-reported Practices of Doctors

PubMed Central

Ismaeel, Abdulrahman Y.; Khaja, Khalid A.J. Al; Damanhori, Awatif H.H.; Sequeira, Reginald P.; Botta, Giuseppe A.

2007-01-01

This nationwide study was conducted to assess the extent of adherence of primary-care physicians to the World Health Organization (WHO)-recommended guidelines on the use of oral rehydration therapy (ORT), antimicrobials, and prescribing of other drugs used in treating symptoms of acute diarrhoea in Bahrain. A questionnaire-based, cross-sectional survey was carried out in primary-care health centres. During a six-week survey period (15 August–30 September 2003), 328 (25.2%) completed questionnaires were returned from 17 of 20 health centres. In a sample of 300 patients, oral rehydration salts (ORS) solution was prescribed to 89.3% (n=268) patients; 12.3% received ORS alone, whereas 77% received ORS in combination with symptomatic drugs. Antimicrobials were prescribed to 2% of the patients. In 11.4% of the cases, rehydration fluids and other drugs were given parenterally. The mean number of drugs was 2.2+0.87 per prescription. In approximately one-third of the patients, three or more drugs were used. Primary-care physicians almost always adhered to the WHO guidelines with respect to ORT and antimicrobials. However, in several instances, ORT was prescribed along with polypharmacy, including irrational use of drugs for symptomatic relief. Effective health policies are needed to reduce the unnecessary burden on the healthcare system. PMID:17985822

A Possible Phenomenon of Persistence in Pseudomonas aeruginosa Treated with Methylene Blue and Red Light.

PubMed

Forte Giacobone, Ana Florencia; Ruiz Gale, Maria Fernanda; Hogert, Elsa Noemí; Oppezzo, Oscar Juan

2016-09-01

Planktonic Pseudomonas aeruginosa cells harvested in stationary phase were exposed to red light in the presence of methylene blue to study the potential occurrence of persistence in bacterial populations submitted to photodynamic antimicrobial therapy. Survival curves revealed the existence of small subpopulations of cells exhibiting increased ability to tolerate the treatment. These subpopulations were detected even using high concentrations of photosensitizer, whether added in a single step or following a fractionated scheme, and when the irradiation medium was modified to delay the photodecomposition of methylene blue. When cells grown from survivors to the treatment were cultured and exposed to red light and dye, their responses were similar to that of the original strain. These results exclude exhaustion of the photosensitizer and selection of resistant mutants as explanations for the features of the survival curves. Cells able to tolerate the treatment were found even when radiation was imparted at a high-dose rate. They exhibit a response typical of persisters, which tolerate antimicrobial agents due to transient and reversible changes in their phenotype, suggesting that persistence is a factor to consider upon evaluating the efficacy of photodynamic antimicrobial therapy. © 2016 The American Society of Photobiology.

Randomized in vivo evaluation of photodynamic antimicrobial chemotherapy on deciduous carious dentin

NASA Astrophysics Data System (ADS)

Steiner-Oliveira, Carolina; Longo, Priscila Larcher; Aranha, Ana Cecília Corrêa; Ramalho, Karen Müller; Mayer, Marcia Pinto Alves; de Paula Eduardo, Carlos

2015-10-01

The aim of this randomized in vivo study was to compare antimicrobial chemotherapies in primary carious dentin. Thirty-two participants ages 5 to 7 years underwent partial caries removal from deep carious dentin lesions in primary molars and were subsequently divided into three groups: control [chlorhexidine and resin-modified glass ionomer cement (RMGIC)], LEDTB [photodynamic antimicrobial chemotherapy (PACT) with light-emitting diode associated with toluidine blue solution and RMGIC], and LMB [PACT with laser associated with methylene blue solution and RMGIC]. The participants were submitted to initial clinical and radiographic examinations. Demographic features and biofilm, gingival, and DMFT/DMFS indexes were evaluated, in addition to clinical and radiographic followups at 6 and 12 months after treatments. Carious dentin was collected before and after each treatment, and the number of Streptococcus mutans, Streptococcus sobrinus, Lactobacillus casei, Fusobacterium nucleatum, Atopobium rimae, and total bacteria was established by quantitative polymerase chain reaction. No signs of pain or restoration failure were observed. All therapies were effective in reducing the number of microorganisms, except for S. sobrinus. No statistical differences were observed among the protocols used. All therapies may be considered as effective modern approaches to minimal intervention for the management of deep primary caries treatment.

Topical application of probiotics in skin: adhesion, antimicrobial and antibiofilm in vitro assays.

PubMed

Lopes, E G; Moreira, D A; Gullón, P; Gullón, B; Cardelle-Cobas, A; Tavaria, F K

2017-02-01

When skin dysbiosis occurs as a result of skin disorders, probiotics can act as modulators, restoring microbial balance. Several properties of selected probiotics were evaluated so that their topical application could be considered. Adhesion, antimicrobial, quorum sensing and antibiofilm assays were carried out with several probiotic strains and tested against selected skin pathogens. All tested strains displayed significant adhesion to keratin. All lactobacilli with the exception of Lactobacillus delbrueckii, showed antimicrobial activity against skin pathogens, mainly due to organic acid production. Most of them also prevented biofilm formation, but only Propioniferax innocua was able to break down mature biofilms. This study demonstrates that although all tested probiotics adhered to human keratin, they showed limited ability to prevent adhesion of some potential skin pathogens. Most of the tested probiotics successfully prevented biofilm formation, suggesting that they may be successfully used in the future as a complement to conventional therapies in the treatment of a range of skin disorders. The topically used probiotics may be a natural, targeted treatment approach to several skin disorders and a complement to conventional therapies which present many undesirable side effects. © 2016 The Society for Applied Microbiology.

Antimicrobial stewardship program in a Malaysian district hospital: First year experience

PubMed Central

Sing, Diana Yap Fui; Boo, Yang Liang; Mukhlis, Roshalina; Chin, Pek Woon; Hoo, Fan Kee

2016-01-01

Backgrounds & Objective: Antimicrobial resistance is an alarming public health threat that requires urgent global solution. Implementation of antimicrobial stewardship program (ASP) is an essential practice element for healthcare institutions in gate-keeping judicious antimicrobial use. This study highlighted the development, first year experience, and result of the implementation of ASP utilizing persuasive and restrictive approaches in a Malaysian district hospital. Methods: An observational study was conducted between January 2015 to December 2015 on implementation of ASP among hospitalized inpatients age 12 years old and above. Results: Recommendations were provided for 60% of cases (110 patients) with the average acceptance rate of 83.33%. Majority of the interventions were to stop the antimicrobial therapy (30.3%), and the most common audited antimicrobials was Piperacillin/Tazobactam (25.5%), followed by Meropenem (11.82%), Amoxicillin/Clavulanate and Vancomycin (8.18%) respectively. The concordance rate towards authorization policy was increased in 2015 (71.59% of cases) as compared before the implementation of ASP in 2014 (60.6% of cases). Restrictive enforcement under ASP had been shown to improve significantly adherence rate towards antimicrobials authorization policy (p-value: 0.004). Conclusion: ASP was successfully implemented in a district hospital. Future studies on its clinical outcomes are important to evaluate its effectiveness as well as focus on the improvement to the pre-existing strategies and measures. PMID:27648056

Application of a nanotechnology antimicrobial spray to prevent lower urinary tract infection: a multicenter urology trial

PubMed Central

2012-01-01

Background Catheter-associated urinary tract infection (CAUTI) is a common nosocomial device-associated infection. It is now recognized that the high infection rates were caused by the formation of biofilm on the surface of the catheters that decreases the susceptibility to antibiotics and results in anti-microbial resistance. In this study, we performed an in vitro test to explore the mechanism of biofilm formation and subsequently conducted a multi-center clinical trial to investigate the efficacy of CAUTI prevention with the application of JUC, a nanotechnology antimicrobial spray. Methods Siliconized latex urinary catheters were cut into fragments and sterilized by autoclaving. The sterilized sample fragments were randomly divided into the therapy and control group, whereby they were sprayed with JUC and distilled water respectively and dried before use. The experimental standard strains of Escherichia coli (E. coli) were isolated from the urine samples of patients. At 16 hours and 7 days of incubation, the samples were extracted for confocal laser scanning microscopy. A total of 1,150 patients were accrued in the clinical study. Patients were randomized according to the order of surgical treatment. The odd array of patients was assigned as the therapy group (JUC), and the even array of patients was assigned as the control group (normal saline). Results After 16 hours of culture, bacterial biofilm formed on the surface of sample fragments from the control group. In the therapy group, no bacterial biofilm formation was observed on the sample fragments. No significant increase in bacterial colony count was observed in the therapy group after 7 days of incubation. On the 7th day of catheterization, urine samples were collected for bacterial culture before extubation. Significant difference was observed in the incidence of bacteriuria between the therapy group and control group (4.52% vs. 13.04%, p < 0.001). Conclusions In this study, the effectiveness of JUC in preventing CAUTI in a hospital setting was demonstrated in both in vitro and clinical studies. PMID:23046566

Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection

NASA Astrophysics Data System (ADS)

Gupta, Akash; Saleh, Neveen M.; Das, Riddha; Landis, Ryan F.; Bigdeli, Arafeh; Motamedchaboki, Khatereh; Rosa Campos, Alexandre; Pomeroy, Kenneth; Mahmoudi, Morteza; Rotello, Vincent M.

2017-06-01

Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. Antibiotic treatment of resistant infections further contributes to the rapidly increasing number of antibiotic-resistant species and strains. Synthetic macromolecules such as nanoparticles (NPs) exhibit broad-spectrum activity against MDR species, however lack of specificity towards bacteria relative to their mammalian hosts limits their widespread therapeutic application. Here, we demonstrate synergistic antimicrobial therapy using hydrophobically functionalized NPs and fluoroquinolone antibiotics for treatment of MDR bacterial strains. An 8-16-fold decrease in antibiotic dosage is achieved in presence of engineered NPs to combat MDR strains. This strategy demonstrates the potential of using NPs to ‘revive’ antibiotics that have been rendered ineffective due to the development of resistance by pathogenic bacteria.

Conventional and molecular diagnostic strategies for prosthetic joint infections.

PubMed

Esteban, Jaime; Sorlí, Luisa; Alentorn-Geli, Eduard; Puig, Lluís; Horcajada, Juan P

2014-01-01

An accurate diagnosis of prosthetic joint infection (PJI) is the mainstay for an optimized clinical management. This review analyzes different diagnostic strategies of PJI, with special emphasis on molecular diagnostic tools and their current and future applications. Until now, the culture of periprosthetic tissues has been considered the gold standard for the diagnosis of PJI. However, sonication of the implant increases the sensitivity of those cultures and is being increasingly adopted by many centers. Molecular diagnostic methods compared with intraoperative tissue culture, especially if combined with sonication, have a higher sensitivity, a faster turnaround time and are not influenced by previous antimicrobial therapy. However, they still lack a system for detection of antimicrobial susceptibility, which is crucial for an optimized and less toxic therapy of PJI. More studies are needed to assess the clinical value of these methods and their cost-effectiveness.

Abdominal Sepsis.

PubMed

De Waele, Jan J

2016-08-01

Abdominal infections are an important challenge for the intensive care physician. In an era of increasing antimicrobial resistance, selecting the appropriate regimen is important and, with new drugs coming to the market, correct use is important more than ever before and abdominal infections are an excellent target for antimicrobial stewardship programs. Biomarkers may be helpful, but their exact role in managing abdominal infections remains incompletely understood. Source control also remains an ongoing conundrum, and evidence is increasing that its importance supersedes the impact of antibiotic therapy. New strategies such as open abdomen management may offer added benefit in severely ill patients, but more data are needed to identify its exact role. The role of fungi and the need for antifungal coverage, on the other hand, have been investigated extensively in recent years, but at this point, it remains unclear who requires empirical as well as directed therapy.

Chromobacterium Violaceum Sepsis: Rethinking Conventional Therapy to Improve Outcome.

PubMed

Richard, Kathleen R; Lovvorn, Joshua J; Oliver, Sara E; Ross, Shannon A; Benner, Kim W; Kong, Michele Y F

2015-10-19

Chromobacterium violaceum (C. violaceum) is a facultative anaerobic gram-negative bacterium found in soil and water, especially in tropical and subtropical areas. Although infection in humans is rare, it is associated with significant morbidity. The bacterium is known for its resistance to multiple antimicrobials, and the possibility of relapse and reinfection. Presence of bacteremia, disseminated infection, and ineffective antimicrobial agents are predictors of mortality. We report the case of a previously healthy 11-year-old male with C. violaceum sepsis who was exposed to stagnant water. He presented with severe septic shock and developed multi-organ system failure. Initial presumptive diagnosis was staphylococcal infection secondary to presence of skin abscesses resulting in antibiotic coverage with vancomycin, clindamycin, nafcillin and ceftriaxone. He also had multiple lung and liver abscesses. Once C. violaceum was identified, he received meropenem and ciprofloxacin, and was later discharged on ertapenem and trimethoprim-sulfamethoxazole (TMP-SMX) to complete a total of six months of antibiotics. He was diagnosed with chronic granulomatous disease (CGD) and is currently on prophylactic TMP-SMX and itraconazole. He has not had any relapses since his initial presentation. This case highlights the importance of considering C. violaceum as a relevant human pathogen, and considering it early in temperate regions, particularly in cases of fulminant sepsis associated with multi-organ abscesses. Once C. violaceum is identified, appropriate antimicrobial therapy should be started promptly, and sufficient duration of treatment is necessary for successful therapy.

Development of shampoo, soap and ointment formulated by green synthesised silver nanoparticles functionalised with antimicrobial plants oils in veterinary dermatology: treatment and prevention strategies.

PubMed

Bansod, Sunita Dashrath; Bawaskar, Manisha Subrashrao; Gade, Aniket Krishnarao; Rai, Mahendra Kumar

2015-08-01

Many scientists have focused their research on the role of nanotechnology for the control of human pathogens, but there are also many topical pathogens present in animals, which infect animals and transfer to humans. Topical therapy is extremely important for the management of dermatological condition in animals. Therefore, the present study aims to evaluate the efficacy of biogenic silver nanoparticles (AgNPs) in combination with herbal oils against animal skin infections which may be responsible for causing infections in human beings. Here, the authors synthesised and characterised the AgNPs from Azadirachta indica. The oils were extracted from medicinal plants including Cymbopogon citratus, Cymbopogon martini, Eucalyptus globules, A. indica and Ocimum sanctum and the antifungal and antibacterial activity of plant oils along with AgNPs were evaluated. An excision wound model was used for the study of wound healing activity in rabbits. AgNPs functionalised oil has demonstrated remarkable antimicrobial activity against pathogens present on the skin of animals. The nano-functionalised antimicrobial oils were used in the formulation of shampoo, soap and ointment for veterinary dermatology. Antimicrobial products of plant origin with AgNPs are valuable, safe and have a specific role in controlling diseases. The authors believe that this approach will be a good alternative therapy to solve the continuous antibiotic resistance developed by many bacterial pathogens and will be utilised in various animal contacting areas in medicine.

Investigation of antimicrobial use at a tertiary care hospital in Southern Punjab, Pakistan using WHO methodology.

PubMed

Atif, Muhammad; Azeem, Muhammad; Saqib, Anum; Scahill, Shane

2017-01-01

Globally, between 20 to 50% of antimicrobial consumption is inappropriate, causing significant impact on the quality of care, cost of therapy and incidence of adverse drug reactions. The purpose of this study was to investigate the prescribing patterns and utilization of antimicrobials in ten selected wards at Bahawal Victoria Hospital (BVH), Bahawalpur, Punjab, Pakistan. A descriptive cross-sectional study was designed using the World Health Organization (WHO) indicators for antimicrobial use. Standard data collection forms were used in ten wards and the Pharmacy Department at BVH. Antimicrobial utilization patterns in terms of frequency and percentage were also determined. Systematic random sampling techniques were used to collect data from 1,000 prescription records out of 21,115 prescriptions written for the six months January to June 2016. For the hospital indicators, a formulary list or essential medicines list (FL/EML) was available, but standard treatment guidelines (STGs) for infectious diseases was not. The average number of days that key antimicrobials were out of stock was 3.3 days per month. The expenditure on antimicrobials as a percentage of the total medicines costs was 12.2%. For the prescribing indicators, the percentage of hospitalizations with antimicrobial(s) prescribed was 82.3%, and the average number of antimicrobials per hospitalization was 1.4 (SD = 0.6). The average duration of antimicrobial treatment per hospitalization was 5.4 days (SD = 3.2). The average cost of antimicrobials prescribed per hospitalization was USD 5.4 (SD = 6.7). None of the patients who were prescribed antimicrobials, received AM according to the STGs (pneumonia and cesarean section cases). Among the patient-care and supplemental indicators, the average duration of hospital stay of patients who received antimicrobials was 6.4 (SD = 4.3) days. The drug sensitivity testing was almost non-existent, with only 0.24% prescription records having drug sensitivity tests. Ceftriaxone (39.6%), metronidazole (23.4%) and cefotaxime (23.1%) were the top most frequently prescribed antimicrobials. The results of the current study revealed less than optimal antimicrobial prescribing and utilization patterns of selected wards at BVH. Continuous education and training of physicians, and cost-effective policies could play an important role in promoting the rational use of antimicrobials in this setting.

Impact of a clinical microbiology-intensive care consulting program in a cardiothoracic intensive care unit.

PubMed

Arena, Fabio; Scolletta, Sabino; Marchetti, Luca; Galano, Angelo; Maglioni, Enivarco; Giani, Tommaso; Corsi, Elisabetta; Lombardi, Silvia; Biagioli, Bonizella; Rossolini, Gian Maria

2015-09-01

A preintervention-postintervention study was carried out over a 4-year period to assess the impact of an antimicrobial stewardship intervention, based on clinical microbiologist ward rounds (clinical microbiology-intensive care partnership [CMICP]), at a cardiothoracic intensive care unit. Comparison of clinical data for 37 patients with diagnosis of bacteremia (18 from preintervention period, 19 from postintervention period) revealed that CMICP implementation resulted in (1) significant increase of appropriate empirical treatments (+34%, P = .029), compliance with guidelines (+28%, P = .019), and number of de-escalations (+42%, P = .032); and (2) decrease (average = 2.5 days) in time to optimization of antimicrobial therapy and levofloxacin (Δ 2009-2012 = -74 defined daily dose [DDD]/1,000 bed days) and teicoplanin (Δ 2009-2012 = -28 DDD/1,000 bed days) use. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Expression of Antimicrobial Peptides by Uveal and Cutaneous Melanoma Cells and Investigation of Their Role in Tumor Cell Migration and Vasculogenic Mimicry.

PubMed

Manarang, Joseph C; Otteson, Deborah C; McDermott, Alison M

2017-11-01

Antimicrobial peptides (AMPs) have been implicated in the pathogenesis of several cancers, although there is also evidence suggesting potential for novel, AMP-based antitumor therapies. Discerning potential roles of AMPs in tumor pathogenesis may provide valuable insight into the mechanisms of novel AMP-based antitumor therapy. mRNA expression of the AMPs α defensin (HNP-1); cathelicidin (LL-37); and β defensins (hBD-1, hBD-2, hBD-3, hBD-4) in human uveal and cutaneous melanoma cell lines, primary human uveal melanocytes, and primary human uveal melanoma cells was determined by reverse transcriptase polymerase chain reaction. An in vitro scratch assay and custom Matlab analysis were used to determine the AMP effects on melanoma cell migration. Last, the effect of specific AMPs on vasculogenic mimicry was determined by three-dimensional (3D) culture and light and fluorescence microscopy. Low-to-moderate AMP transcript levels were detected, and these varied across the cells tested. Overall, LL-37 expression was increased while hBD-4 was decreased in most melanoma cell lines, compared to primary cultured uveal melanocytes. There was no observable influence of HNP-1 and LL-37 on tumor cell migration. Additionally, aggressive cutaneous melanoma cells grown in 3D cultures exhibited vasculogenic mimicry, although AMP exposure did not alter this process. Collectively, our data show that although AMP mRNA expression is variable between uveal and cutaneous melanoma cells, these peptides have little influence on major characteristics that contribute to tumor aggressiveness and progression.

Pathogen Identification by Multiplex LightMix Real-Time PCR Assay in Patients with Meningitis and Culture-Negative Cerebrospinal Fluid Specimens

PubMed Central

Wagner, Karoline; Springer, Burkard; Pires, Valeria P.

2017-01-01

ABSTRACT Acute bacterial meningitis is a medical emergency, and delays in initiating effective antimicrobial therapy result in increased morbidity and mortality. Culture-based methods, thus far considered the “gold standard” for identifying bacterial microorganisms, require 24 to 48 h to provide a diagnosis. In addition, antimicrobial therapy is often started prior to clinical sample collection, thereby decreasing the probability of confirming the bacterial pathogen by culture-based methods. To enable a fast and accurate detection of the most important bacterial pathogens causing meningitis, namely, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Streptococcus agalactiae, and Listeria monocytogenes, we evaluated a commercially available multiplex LightMix real-time PCR (RT-PCR) in 220 cerebrospinal fluid (CSF) specimens. The majority of CSF samples were collected by lumbar puncture, but we also included some CSF samples from patients with symptoms of meningitis from the neurology department that were recovered from shunts. CSF samples were analyzed by multiplex RT-PCR enabling a first diagnosis within a few hours after sample arrival at our institute. In contrast, bacterial identification took between 24 and 48 h by culture. Overall, a high agreement of bacterial identification between culture and multiplex RT-PCR was observed (99%). Moreover, multiplex RT-PCR enabled the detection of pathogens, S. pneumoniae (n = 2), S. agalactiae (n = 1), and N. meningitidis (n = 1), in four culture-negative samples. As a complement to classical bacteriological CSF culture, the LightMix RT-PCR assay proved to be valuable by improving the rapidity and accuracy of the diagnosis of bacterial meningitis. PMID:29237781

Diabetic foot infections: Current treatment and delaying the 'post-antibiotic era'.

PubMed

Lipsky, Benjamin A

2016-01-01

Treatment for diabetic foot infections requires properly diagnosing infection, obtaining an appropriate specimen for culture, assessing for any needed surgical procedures and selecting an empiric antibiotic regimen. Therapy will often need to be modified based on results of culture and sensitivity testing. Because of excessive and inappropriate use of antibiotics for treating diabetic foot infections, resistance to the usually employed bacteria has been increasing to alarming levels. This article reviews recommendations from evidence-based guidelines, informed by results of systematic reviews, on treating diabetic foot infections. Data from the pre-antibiotic era reported rates of mortality of about 9% and of high-level leg amputations of about 70%. Outcomes have greatly improved with appropriate antibiotic therapy. While there are now many oral and parenteral antibiotic agents that have demonstrated efficacy in treating diabetic foot infections, the rate of infection with multidrug-resistant pathogens is growing. This problem requires a multi-focal approach, including providing education to both clinicians and patients, developing robust antimicrobial stewardship programmes and using new diagnostic and therapeutic technologies. Recently, new methods have been developed to find novel antibiotic agents and to resurrect old treatments, like bacteriophages, for treating these difficult infections. Medical and political leaders have recognized the serious global threat posed by the growing problem of antibiotic resistance. By a multipronged approach that includes exerting administrative pressure on clinicians to do the right thing, investing in new technologies and encouraging the profitable development of new antimicrobials, we may be able to stave off the coming 'post-antibiotic era'. Copyright © 2016 John Wiley & Sons, Ltd.

Nanoparticle Stabilized Liposomes for Acne Therapy

NASA Astrophysics Data System (ADS)

Fu, Victoria

Acne vulgaris is a common skin disease that affects over 40 million people in the United States alone. The main cause of acne vulgaris is Propionibacterium acnes (P. acnes), resides deep in the pores and follicles of the skin in order to feed on oil produced by the sebaceous glands. The liposome is a lipid based nanoparticle with numerous advantages over free drug molecules as an acne treatment alternative. Bare liposomes loaded with lauric acid (LipoLA) were found to show strong antimicrobial activity against P. acnes while generating minimal toxicity. However, the platform is limited by the spontaneous tendency of liposomes to fuse with each other. Attaching nanoparticles to the surface of liposomes can overcome this challenge by providing steric repulsion and reduce surface tension. Thus, carboxyl-functionalized gold nanoparticles (AuC) were attached to the surface of liposomes (AuC-liposomes) loaded with doxycycline, a general tetracycline antibiotic. These particles were found to have a diameter of 120 nm and a zeta potential of 20.0 mV. Both fluorescent and antimicrobial studies demonstrated that based on electrostatic interaction, negatively charged AuC attached to the liposome's positively charged surface and stabilized liposomes in a neutral pH environment (pH = 7.4). Upon entering the skin's acidic environment (pH = 4), AuC detached from the liposome's surface and liposomes could fuse with P. acnes residing in the pores. Furthermore, toxicity studies showed that AuC-liposomes did not induce any significant toxicity, while two of the leading over-the-counter therapies, benzoyl peroxide and salicylic acid, generated substantial skin irritation.

Important cellular targets for antimicrobial photodynamic therapy.

PubMed

Awad, Mariam M; Tovmasyan, Artak; Craik, James D; Batinic-Haberle, Ines; Benov, Ludmil T

2016-09-01

The persistent problem of antibiotic resistance has created a strong demand for new methods for therapy and disinfection. Photodynamic inactivation (PDI) of microbes has demonstrated promising results for eradication of antibiotic-resistant strains. PDI is based on the use of a photosensitive compound (photosensitizer, PS), which upon illumination with visible light generates reactive species capable of damaging and killing microorganisms. Since photogenerated reactive species are short lived, damage is limited to close proximity of the PS. It is reasonable to expect that the larger the number of damaged targets is and the greater their variety is, the higher the efficiency of PDI is and the lower the chances for development of resistance are. Exact molecular mechanisms and specific targets whose damage is essential for microbial inactivation have not been unequivocally established. Two main cellular components, DNA and plasma membrane, are regarded as the most important PDI targets. Using Zn porphyrin-based PSs and Escherichia coli as a model Gram-negative microorganism, we demonstrate that efficient photoinactivation of bacteria can be achieved without detectable DNA modification. Among the cellular components which are modified early during illumination and constitute key PDI targets are cytosolic enzymes, membrane-bound protein complexes, and the plasma membrane. As a result, membrane barrier function is lost, and energy and reducing equivalent production is disrupted, which in turn compromises cell defense mechanisms, thus augmenting the photoinduced oxidative injury. In conclusion, high PDI antimicrobial effectiveness does not necessarily require impairment of a specific critical cellular component and can be achieved by inducing damage to multiple cellular targets.

Antimicrobial blue light inactivation of Pseudomonas aeruginosa by photo-excitation of endogenous porphyrins: In vitro and in vivo studies.

PubMed

Amin, Rehab M; Bhayana, Brijesh; Hamblin, Michael R; Dai, Tianhong

2016-07-01

Pseudomonas aeruginosa is among the most common pathogens that cause nosocomial infections and is responsible for about 10% of all hospital-acquired infections. In the present study, we investigated the potential development of tolerance of P. aeruginosa to antimicrobial blue light by carrying 10 successive cycles of sublethal blue light inactivation. The high-performance liquid chromatographic (HPLC) analysis was performed to identify endogenous porphyrins in P. aeruginosa cells. In addition, we tested the effectiveness of antimicrobial blue light in a mouse model of nonlethal skin abrasion infection by using a bioluminescent strain of P. aeruginosa. The results demonstrated that no tolerance was developed to antimicrobial blue light in P. aeruginosa after 10 cycles of sub-lethal inactivation. HPLC analysis showed that P. aeruginosa is capable of producing endogenous porphyrins in particularly, coproporphyrin III, which are assumed to be responsible for the photodynamic effects of blue light alone. P. aeruginosa infection was eradicated by antimicrobial blue light alone (48 J/cm(2) ) without any added photosensitizer molecules in the mouse model. In conclusion, endogenous photosensitization using blue light should gain considerable attention as an effective and safe alternative antimicrobial therapy for skin infections. Lasers Surg. Med. 48:562-568, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of ionic strength on the antimicrobial photodynamic efficiency of methylene blue.

PubMed

Núñez, Silvia Cristina; Garcez, Aguinaldo Silva; Kato, Ilka Tiemy; Yoshimura, Tania Mateus; Gomes, Laércio; Baptista, Maurício Silva; Ribeiro, Martha Simões

2014-03-01

Antimicrobial photodynamic therapy (APDT) may become a useful clinical tool to treat microbial infections, and methylene blue (MB) is a well-known photosensitizer constantly employed in APDT studies, and although MB presents good efficiency in antimicrobial studies, some of the MB photochemical characteristics still have to be evaluated in terms of APDT. This work aimed to evaluate the role of MB solvent's ionic strength regarding dimerization, photochemistry, and photodynamic antimicrobial efficiency. Microbiological survival fraction assays on Escherichia coli were employed to verify the solution's influence on MB antimicrobial activity. MB was evaluated in deionized water and 0.9% saline solution through optical absorption spectroscopy; the solutions were also analysed via dissolved oxygen availability and reactive oxygen species (ROS) production. Our results show that bacterial reduction was increased in deionized water. Also we demonstrated that saline solution presents less oxygen availability than water, the dimer/monomer ratio for MB in saline is smaller than in water and MB presented a higher production of ROS in water than in 0.9% saline. Together, our results indicate the importance of the ionic strength in the photodynamic effectiveness and point out that this variable must be taken into account to design antimicrobial studies and to evaluate similar studies that might present conflicting results.

Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients: Challenges and Drug Delivery Approaches

PubMed Central

Kłodzińska, Sylvia Natalie; Priemel, Petra Alexandra; Rades, Thomas; Mørck Nielsen, Hanne

2016-01-01

Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa infections in CF patients are focused mainly on the delivery of antimicrobials to the lower respiratory tract, disregarding the sinuses. However, the sinuses constitute a reservoir for P. aeruginosa growth, leading to re-infection of the lungs, even after clearing an initial lung infection. Eradication of P. aeruginosa from the respiratory tract after a first infection has been shown to delay chronic pulmonary infection with the bacteria for up to two years. The challenges with providing a suitable treatment for bacterial sinusitis include: (i) identifying a suitable antimicrobial compound; (ii) selecting a suitable device to deliver the drug to the sinuses and nasal cavities; and (iii) applying a formulation design, which will mediate delivery of a high dose of the antimicrobial directly to the site of infection. This review highlights currently available inhalable antimicrobial formulations for treatment and management of biofilm infections caused by P. aeruginosa and discusses critical issues related to novel antimicrobial drug formulation design approaches. PMID:27735846

Antimicrobial activity of ProRoot MTA in contact with blood

PubMed Central

Farrugia, C.; Baca, P.; Camilleri, J.; Arias Moliz, M. T.

2017-01-01

Dental materials based on Portland cement, which is used in the construction industry have gained popularity for clinical use due to their hydraulic properties, the interaction with tooth tissue and their antimicrobial properties. The antimicrobial properties are optimal in vitro. However in clinical use contact with blood may affect the antimicrobial properties. This study aims to assess whether antimicrobial properties of the Portland cement-based dental cements such as mineral trioxide aggregate (MTA) are also affected by contact with blood present in clinical situations. ProRoot MTA, a Portland cement-based dental cement was characterized following contact with water, or heparinized blood after 1 day and 7 days aging. The antimicrobial activity under the mentioned conditions was assessed using 3 antimicrobial tests: agar diffusion test, direct contact test and intratubular infection test. MTA in contact with blood was severely discoloured, exhibited an additional phosphorus peak in elemental analysis, no calcium hydroxide peaks and no areas of bacterial inhibition growth in the agar diffusion test were demonstrated. ProRoot MTA showed limited antimicrobial activity, in both the direct contact test and intratubular infection test. When aged in water ProRoot MTA showed higher antimicrobial activity than when aged in blood. Antimicrobial activity reduced significantly after 7 days. Further assessment is required to investigate behaviour in clinical situations. PMID:28128328

A comparison of the effect of short-acting and long-acting cloxacillin-based dry-cow therapy on somatic cell counts after calving in cows also given internal teat sealants.

PubMed

Whitfield, L K; Laven, R A

2018-01-01

To compare, in cows treated with an internal teat sealant, the effect of short-acting and long-acting cloxacillin-based dry-cow therapy on somatic cell counts (SCC) after calving. Cows from a spring-calving, pasture-based dairy farm in the Manawatu-Whanganui region of New Zealand were randomly allocated to receive either a short-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=291) or a long-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=288) at the end of lactation. Cows were managed on-farm with routine husbandry procedures through the dry period and following calving. A multivariable logistic regression model was used to determine the association between length of action of dry-cow therapy and the proportion of cows with a SCC >150,000 cells/mL at the first herd test after calving. Age of cow, mean SCC for the preceding season and interval from calving to the first post-calving herd test were all associated with the proportion of cows with an individual SCC >150,000 cells/mL at the first herd test (p<0.001) Treatment with the short-acting dry-cow therapy was not associated with decreased odds of cows having a SCC >150,000 cells/mL at the first herd test compared with treatment with long-acting dry-cow therapy (OR=0.724; 95% CI=0.40-1.30). In this herd, which routinely used internal teat sealants, the use of short-acting cloxacillin-based dry-cow therapy did not result in an increased proportion of cows with elevated SSC post-calving. This was a single farm, single year study but indicates that in this herd, changing from a long-acting to a short-acting antimicrobial may have no impact on the prevalence of subclinical mastitis.

Two-Drug Antimicrobial Chemotherapy: A Mathematical Model and Experiments with Mycobacterium marinum

PubMed Central

Ankomah, Peter; Levin, Bruce R.

2012-01-01

Multi-drug therapy is the standard-of-care treatment for tuberculosis. Despite this, virtually all studies of the pharmacodynamics (PD) of mycobacterial drugs employed for the design of treatment protocols are restricted to single agents. In this report, mathematical models and in vitro experiments with Mycobacterium marinum and five antimycobacterial drugs are used to quantitatively evaluate the pharmaco-, population and evolutionary dynamics of two-drug antimicrobial chemotherapy regimes. Time kill experiments with single and pairs of antibiotics are used to estimate the parameters and evaluate the fit of Hill-function-based PD models. While Hill functions provide excellent fits for the PD of each single antibiotic studied, rifampin, amikacin, clarithromycin, streptomycin and moxifloxacin, two-drug Hill functions with a unique interaction parameter cannot account for the PD of any of the 10 pairs of these drugs. If we assume two antibiotic-concentration dependent functions for the interaction parameter, one for sub-MIC and one for supra-MIC drug concentrations, the modified biphasic Hill function provides a reasonably good fit for the PD of all 10 pairs of antibiotics studied. Monte Carlo simulations of antibiotic treatment based on the experimentally-determined PD functions are used to evaluate the potential microbiological efficacy (rate of clearance) and evolutionary consequences (likelihood of generating multi-drug resistance) of these different drug combinations as well as their sensitivity to different forms of non-adherence to therapy. These two-drug treatment simulations predict varying outcomes for the different pairs of antibiotics with respect to the aforementioned measures of efficacy. In summary, Hill functions with biphasic drug-drug interaction terms provide accurate analogs for the PD of pairs of antibiotics and M. marinum. The models, experimental protocols and computer simulations used in this study can be applied to evaluate the potential microbiological and evolutionary efficacy of two-drug therapy for any bactericidal antibiotics and bacteria that can be cultured in vitro. PMID:22253599

Amino acid–based surfactants: New antimicrobial agents.

PubMed

Pinazo, A; Manresa, M A; Marques, A M; Bustelo, M; Espuny, M J; Pérez, L

2016-02-01

The rapid increase of drug resistant bacteria makes necessary the development of new antimicrobial agents. Synthetic amino acid-based surfactants constitute a promising alternative to conventional antimicrobial compounds given that they can be prepared from renewable raw materials. In this review, we discuss the structural features that promote antimicrobial activity of amino acid-based surfactants. Monocatenary, dicatenary and gemini surfactants that contain different amino acids on the polar head and show activity against bacteria are revised. The synthesis and basic physico-chemical properties have also been included.

Aberrant lipogenesis is a metabolic marker for azole-resistant candida albicans (Conference Presentation)

NASA Astrophysics Data System (ADS)

Karanja, Caroline; Hong, Weili; Younis, Waleed; Cheng, Ji-Xin; Seleem, Mohamed

2017-02-01

Candida is the single most important cause of fungal bloodstream infections worldwide causing significant mortality as high as 50%. This high mortality rate is, in part, due to the inability to rapidly diagnose and simultaneously initiate an effective antifungal therapy early in the disease process. Current culture-based diagnostics are often slow, requiring several days to complete, and are only 50% sensitive in diagnosing candidemia (Candida bloodstream infection). For every 12 hours of delay in starting correct antifungal therapy, the risk of death for a given patient with candidemia increases by 200%. To address this unmet need, we explored the potential of employing stimulated Raman Scattering (SRS) imaging to diagnose candidemia and probe metabolic differences between resistant and susceptible strain at a single cell level. Metabolism is integral to pathogenicity; microorganism have very short life cycles, and therefore only a few hours are needed to observe a full metabolic cycle. SRS imaging at C-H vibration frequency at 2850 cm-1 revealed a substantial difference in lipogenesis between the susceptible and resistant C. albicans. Treating the C. albicans with fluconazole, an antimicrobial drug that targets ergosterol biosynthesis only affected the lipogenesis in the susceptible strain. Our results show that single-cell metabolic imaging under a SRS microscope can be used for diagnose candidemia and early detection of antimicrobial susceptibility.

Direct identification from positive blood broth culture by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS).

PubMed

Barberino, Maria Goreth; Silva, Marcio de Oliveira; Arraes, Ana Carolina Palmeiras; Correia, Luís Cláudio; Mendes, Ana Verena

Bloodstream infections (BSIs) are among the most concerning bacterial infections. They are one of the leading causes of morbidity and mortality, and occur in 30-70% of critical care patients. The prompt identification of the causative microorganism can help choosing the appropriate antimicrobial therapy that will lead to better clinical outcomes. Blood culture is one of the most relevant tests for microbiological diagnosis of bacterial infections. The introduction of the MALDI-TOF microbiological diagnosis significantly decreased the time of identifying microorganisms. However, it depends on the growth on solid culture medium. In this study, 538 bottles of positive blood cultures were evaluated to test the accuracy of an in house modified protocol. The study sample consisted of 198 Gram-negative and 350 Gram-positive bacteria. In all, 460 (83.94%) species were identified based on the direct plate findings. The protocol allowed the identification of 185/198 (93.43%) of the Gram-negative bacteria, including aerobes, anaerobes, and non-fermenters, and 275/350 (78.85%) of the Gram-positive bacteria. The proposed method has the potential to provide accurate results in comparison to the traditional method with the potential to reduce the turnaround time for the results and optimize antimicrobial therapy in BSI. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Clinical translation of polymyxin-based combination therapy: Facts, challenges and future opportunities.

PubMed

Zhang, Xueli; Guo, Fengmei; Shao, Hua; Zheng, Xiao

2017-02-01

The emergence and spread of multidrug resistant Gram-negative bacteria has led to a resurgence in the clinical use of polymyxin antibiotics. However, the prevalence of polymyxin resistance is on the rise at an alarming rate, motivating the idea of combination therapy to sustain the revival of these "old" antibiotics. Although ample evidence in favor of combination therapy has emerged, it seems impracticable and confusing to find a promising combination from the diverse reports or gain adequate information on the efficacy and safety profile. With a stagnating discovery pipeline of novel antimicrobials, there is a clear need to fill the knowledge gaps in translating these basic research data to beneficial clinical practice. In this review, we examined the factors and ambiguities that stand as major hurdles in bringing polymyxin combination therapy to bedside care, highlighting the importance and urgency of incorporating translational research insights into areas of difficulty. We also discussed future research priorities that are essential to gather the necessary evidence and insights for promoting the best possible use of polymyxins in combination therapy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Antimicrobial susceptibilities and population structure of Staphylococcus epidermidis associated with ovine mastitis.

PubMed

Onni, Toniangelo; Sanna, Giovanna; Larsen, Jesper; Tola, Sebastiana

2011-02-24

Intramammary infections are a serious problem for dairy sheep farms, and Staphylococcus epidermidis is one of the main etiological agents of ovine mastitis. In this work, 131 S. epidermidis isolates, collected from 2201 dairy Sarda sheep belonging to 14 flocks with high somatic cell count scores, were studied. The flocks were located in diverse geographical areas of Sardinia, Italy. The aim of study was to assess the susceptibility of isolates to 13 antimicrobial agents, many of which are frequently used in mastitis therapy. Oxacillin was used for detecting methicillin-resistant S. epidermidis (MRSE) by disk diffusion test. Thirty-eight percent of the isolates (n=50) were resistant to penicillin, 7.6% (n=10) were resistant to tetracycline, and 2.3% (n=3) were resistant to both penicillin and tetracycline (PTRSE). Two isolates were resistant to five antimicrobials including methicillin. Analysis of staphylococcal cassette chromosome mec (SCCmec) elements showed that both MRSE isolates harbored SCCmec type IVa. Based on pulsed-field gel electrophoresis (PFGE) typing by SmaI macrorestriction, S. epidermidis isolates were grouped into four clusters at 75% similarity level. The two multi-drug resistant MRSE isolates displayed distinct PFGE patters. This study indicates that S. epidermidis isolates from sheep milk samples may accumulate resistance markers for different antimicrobial agents. Furthermore, the occurrence of PTRSE and MRSE suggests to adopt adequate hygienic measures when handling animals with intramammary infections, in order to prevent spreading PTRSE and MRSE strains to humans through direct contact and/or consumption of contaminated food. Copyright © 2010 Elsevier B.V. All rights reserved.

Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases).

PubMed

Hillier, Andrew; Lloyd, David H; Weese, J Scott; Blondeau, Joseph M; Boothe, Dawn; Breitschwerdt, Edward; Guardabassi, Luca; Papich, Mark G; Rankin, Shelley; Turnidge, John D; Sykes, Jane E

2014-06-01

Superficial bacterial folliculitis (SBF) is usually caused by Staphylococcus pseudintermedius and routinely treated with systemic antimicrobial agents. Infection is a consequence of reduced immunity associated with alterations of the skin barrier and underlying diseases that may be difficult to diagnose and resolve; thus, SBF is frequently recurrent and repeated treatment is necessary. The emergence of multiresistant bacteria, particularly meticillin-resistant S. pseudintermedius (MRSP), has focused attention on the need for optimal management of SBF. Provision of an internationally available resource guiding practitioners in the diagnosis, treatment and prevention of SBF. The guidelines were developed by the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases, with consultation and advice from diplomates of the American and European Colleges of Veterinary Dermatology. They describe optimal methods for the diagnosis and management of SBF, including isolation of the causative organism, antimicrobial susceptibility testing, selection of antimicrobial drugs, therapeutic protocols and advice on infection control. Guidance is given for topical and systemic modalities, including approaches suitable for MRSP. Systemic drugs are classified in three tiers. Tier one drugs are used when diagnosis is clear cut and risk factors for antimicrobial drug resistance are not present. Otherwise, tier two drugs are used and antimicrobial susceptibility tests are mandatory. Tier three includes drugs reserved for highly resistant infections; their use is strongly discouraged and, when necessary, they should be used in consultation with specialists. Optimal management of SBF will improve antimicrobial use and reduce selection of MRSP and other multidrug-resistant bacteria affecting animal and human health. © 2014 ESVD and ACVD.

Tea tree oil nanoemulsions for inhalation therapies of bacterial and fungal pneumonia.

PubMed

Li, Miao; Zhu, Lifei; Liu, Boming; Du, Lina; Jia, Xiaodong; Han, Li; Jin, Yiguang

2016-05-01

Tea tree oil (TTO) is a natural essential oil with strong antimicrobial efficacy and little drug resistance. However, the biomedical applications of TTO are limited due to its hydrophobicity and formulation problems. Here, we prepared an inhalable TTO nanoemulsion (nanoTTO) for local therapies of bacterial and fungal pneumonia. The optimal formulation of nanoTTOs consisted of TTO/Cremophor EL/water with a mean size of 12.5nm. The nanoTTOs showed strong in vitro antimicrobial activities on Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Candida albicans. After inhalation to the lung, the nanoTTOs had higher anti-fungal effect than fluconazole on the fungal pneumonia rat models with reduced lung injury, highly microbial clearance, blocking of leukocyte recruitment, and decrease of pro-inflammatory mediators. In the case of rat bacterial pneumonia, the nanoTTOs showed slightly lower therapeutic efficacy than penicillin though at a much lower dose. Taken together, our results show that the inhalable nanoTTOs are promising nanomedicines for local therapies of fungal and bacterial pneumonia with no obvious adverse events. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment of chancroid in resource-poor countries.

PubMed

Annan, Naa Torshie; Lewis, David A

2005-04-01

Chancroid, formerly a major cause of the genital ulcer disease syndrome, remains an important cofactor in both the transmission and acquisition of HIV-1 infection. Those countries with the greatest burden of HIV also have some of the highest prevalence rates of chancroid worldwide. The diagnosis of chancroid, caused by the fastidious bacterium Haemophilus ducreyi, is both expensive and difficult in many resource-poor areas. These areas of the world use syndromic management to treat genital ulcers and such an approach has proven effective in reducing rates of bacterial genital ulcer diseases. There are currently inexpensive and effective single-dose therapies available to treat chancroid. Single-dose regimens, given at first presentation, improve compliance and reduce the risk of sexually transmitted infections. Bacterial resistance to several antimicrobial agents has increased over the years and remains a continued threat to effective antimicrobial therapy. Follow-up of cases, and partner notification and treatment is carried out to limit reinfection and onward transmission of chancroid. Patients with coexistent HIV may be particularly at risk of failing single-dose therapy and should therefore be reviewed wherever possible.

Synthesis and structure-activity relationships of novel cationic lipids with anti-inflammatory and antimicrobial activities.

PubMed

Myint, Melissa; Bucki, Robert; Janmey, Paul A; Diamond, Scott L

2015-07-15

Certain membrane-active cationic steroids are known to also possess both anti-inflammatory and antimicrobial properties. This combined functionality is particularly relevant for potential therapies of infections associated with elevated tissue damage, for example, cystic fibrosis airway disease, a condition characterized by chronic bacterial infections and ongoing inflammation. In this study, six novel cationic glucocorticoids were synthesized using beclomethasone, budesonide, and flumethasone. Products were either monosubstituted or disubstituted, containing one or two steroidal groups, respectively. In vitro evaluation of biological activities demonstrated dual anti-inflammatory and antimicrobial properties with limited cytotoxicity for all synthesized compounds. Budesonide-derived compounds showed the highest degree of both glucocorticoid and antimicrobial properties within their respective mono- and disubstituted categories. Structure-activity analyses revealed that activity was generally related to the potency of the parent glucocorticoid. Taken together, these data indicate that these types of dual acting cationic lipids can be synthesized with the appropriate starting steroid to tailor activities as desired. Copyright © 2015 Elsevier Ltd. All rights reserved.

Application of Nanoparticle Technologies in the Combat against Anti-Microbial Resistance

PubMed Central

Kumar, Mayur; Curtis, Anthony

2018-01-01

Anti-microbial resistance is a growing problem that has impacted the world and brought about the beginning of the end for the old generation of antibiotics. Increasingly, more antibiotics are being prescribed unnecessarily and this reckless practice has resulted in increased resistance towards these drugs, rendering them useless against infection. Nanotechnology presents a potential answer to anti-microbial resistance, which could stimulate innovation and create a new generation of antibiotic treatments for future medicines. Preserving existing antibiotic activity through novel formulation into or onto nanotechnologies can increase clinical longevity of action against infection. Additionally, the unique physiochemical properties of nanoparticles can provide new anti-bacterial modes of action which can also be explored. Simply concentrating on antibiotic prescribing habits will not resolve the issue but rather mitigate it. Thus, new scientific approaches through the development of novel antibiotics and formulations is required in order to employ a new generation of therapies to combat anti-microbial resistance. PMID:29342903

Risk factors for ceftiofur resistance in Escherichia coli from Belgian broilers.

PubMed

Persoons, D; Haesebrouck, F; Smet, A; Herman, L; Heyndrickx, M; Martel, A; Catry, B; Berge, A C; Butaye, P; Dewulf, J

2011-05-01

A cross-sectional study on 32 different Belgian broiler farms was performed in 2007 and 2008 to identify risk factors for ceftiofur resistance in Escherichia coli. On each farm, one E. coli colony was isolated from 30 random birds. Following susceptibility testing of 14 antimicrobials, an on-farm questionnaire was used to obtain information on risk factors. Using a multilevel logistic regression model two factors were identified at the animal level: resistance to amoxicillin and to trimethoprim-sulfonamide. On the farm level, besides antimicrobial use, seven management factors were found to be associated with the occurrence of ceftiofur resistance in E. coli from broilers: poor hygienic condition of the medicinal treatment reservoir, no acidification of drinking water, more than three feed changes during the production cycle, hatchery of origin, breed, litter material used, and treatment with amoxicillin. This study confirms that not only on-farm antimicrobial therapy, but also management- and hatchery-related factors influence the occurrence of antimicrobial resistance.

Recent Advances in Root Canal Disinfection: A Review

PubMed Central

Mohammadi, Zahed; Jafarzadeh, Hamid; Shalavi, Sousan; Palazzi, Flavio

2017-01-01

The microbial biofilm is an important factor for human infection. Finding effective antimicrobial strategies should be considered for decreasing antimicrobial resistance and controlling the infectious diseases. Treatment of infected canal systems may not be able to remove all bacteria and so bacterial persistence after treatment may occur. Application of antibacterial nanoparticles may be a potential strategy to improve the elimination of bacteria from the canal. Furthermore, mechanism of action and applications of photodynamic therapy and Photon-induced photoacoustic streaming (PIPS) and GentleWave system was reviewed. PMID:29225632

Antimicrobial Use for and Resistance of Zoonotic Bacteria Recovered from Nonhuman Primates.

PubMed

Kim, Jeffrey; Coble, Dondrae J; Salyards, Gregory W; Bower, Julie K; Rinaldi, William J; Plauche, Gail B; Habing, Gregory G

2017-02-01

As a growing threat to human and animal health, antimicrobial resistance (AMR) has become a central public-health topic. Largescale surveillance systems, such as the National Antimicrobial Resistance Monitoring System (NARMS), are now established to monitor and provide guidance regarding AMR, but comprehensive literature on AMR among NHP is sparse. This study provides data regarding current antimicrobial use strategies and the prevalence of AMR in zoonotic bacteria recovered from NHP within biomedical research institutions. We focused on 4 enteric bacteria: Shigella flexneri, Yersinia enterocolitica, Y. pseudotuberculosis, and Campylobacter jejuni. Fifteen veterinarians, 7 biomedical research institutions, and 4 diagnostic laboratories participated, providing susceptibility test results from January 2012 through April 2015. Veterinarians primarily treated cases caused by S. flexneri, Y. enterocolitica, and Y. pseudotuberculosis with enrofloxacin but treated C. jejuni cases with azithromycin and tylosin. All isolates were susceptible to the associated primary antimicrobial but often showed resistance to others. Specifically, S. flexneri isolates frequently were resistant to erythromycin (87.5%), doxycycline (73.7%), and tetracycline (38.3%); Y. enterocolitica isolates to ampicillin (100%) and cefazolin (93.6%); and C. jejuni isolates to methicillin (99.5%) and cephalothin (97.5%). None of the 58 Y. pseudotuber-culosis isolates was resistant to any tested antimicrobial. Notably, resistance patterns were not shared between this study's NHP isolates and human isolates presented by NARMS. Our findings indicate that zoonotic bacteria from NHP diagnostic samples are broadly susceptible to the antimicrobials used to treat the clinical infections. These results can help veterinarians ensure effective antimicrobial therapy and protect staff by minimizing occupational risk.

Antimicrobial Use for and Resistance of Zoonotic Bacteria Recovered from Nonhuman Primates

PubMed Central

Kim, Jeffrey; Coble, Dondrae J; Salyards, Gregory W; Bower, Julie K; Rinaldi, William J; Plauche, Gail B; Habing, Gregory G

2017-01-01

As a growing threat to human and animal health, antimicrobial resistance (AMR) has become a central public-health topic. Large-scale surveillance systems, such as the National Antimicrobial Resistance Monitoring System (NARMS), are now established to monitor and provide guidance regarding AMR, but comprehensive literature on AMR among NHP is sparse. This study provides data regarding current antimicrobial use strategies and the prevalence of AMR in zoonotic bacteria recovered from NHP within biomedical research institutions. We focused on 4 enteric bacteria: Shigella flexneri, Yersinia enterocolitica, Y. pseudotuberculosis, and Campylobacter jejuni. Fifteen veterinarians, 7 biomedical research institutions, and 4 diagnostic laboratories participated, providing susceptibility test results from January 2012 through April 2015. Veterinarians primarily treated cases caused by S. flexneri, Y. enterocolitica, and Y. pseudotuberculosis with enrofloxacin but treated C. jejuni cases with azithromycin and tylosin. All isolates were susceptible to the associated primary antimicrobial but often showed resistance to others. Specifically, S. flexneri isolates frequently were resistant to erythromycin (87.5%), doxycycline (73.7%), and tetracycline (38.3%); Y. enterocolitica isolates to ampicillin (100%) and cefazolin (93.6%); and C. jejuni isolates to methicillin (99.5%) and cephalothin (97.5%). None of the 58 Y. pseudotuberculosis isolates was resistant to any tested antimicrobial. Notably, resistance patterns were not shared between this study's NHP isolates and human isolates presented by NARMS. Our findings indicate that zoonotic bacteria from NHP diagnostic samples are broadly susceptible to the antimicrobials used to treat the clinical infections. These results can help veterinarians ensure effective antimicrobial therapy and protect staff by minimizing occupational risk. PMID:28222842

Antimicrobial susceptibility pattern of Klebsiella species from Ebonyi State University Teaching Hospital Abakaliki, Nigeria.

PubMed

Akujobi, C N

2005-12-01

Klesiella specie isolated from clinical specimens from Ebonyi State University Teaching Hospital (EBSUTH). Abakakliki were studied to determine the antimicrobial susceptibility pattern. Between January, 2003 and September 2004 a total of 3.600 specimens processed in the routine Medical Microbiology laboratory of EBSUTH, of which 245(6.8%) yielded Klebsiella species, with 84 from out - patients and 161 from in - patients. The number of isolates from various samples were: Urine 126, Sputum 37 Endocervical swab 13, Aspirates 8, High Vaginal Swab 7, Blood 3, Eye Swab, Ear Swab and Cerebrospinal fluid were 2 samples each. Organisms were identified by conventional methods. Antimicrobial susceptibility was done by the disk diffusion methods. The antimicrobial disk used include: Ceftazidime, Cefuroxime, Cefotaxine, Augmentin, Pefloxacin (30ug), Doxycyline (25ug) Genticin (10 ug) Ciprofloacin and Ofloxacin (5ug) each and Erythromycin (15ug). All were Oxoid products. Results were interpreted according to NCCLS criteria. Klebsilla species were isolated mostly from urine specimens (51.4%) followed by wound swabs (18.4%). Antimicrobial susceptibility to various groups drugs used was generally poor. The most sensitive antimicrobial was Ciprofloxacin with 121(49.4%) isolates susceptible to it, followed by Gentamicin with 95 (38.8%) and Ceftazidime with 90(36.7%). Seventeen isolates were multiresistant to all the antimicrobial agents used. The result of this study will help in the empiric therapy of infection caused by Klebsiella species in Ebonyi State University Teaching Hospital, Abakaliki, Nigeria but continuous surverillance of antimicrobial resistance of the organnisn is very necessary in the formulation of a sound antibiotic policy in the hospital.

Treatment of mastitis during lactation.

PubMed

Pyörälä, S

2009-04-01

Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, because of high treatment costs and generally poor efficacy. All mastitis treatment should be evidence-based, i.e., the efficacy of each product and treatment length should be demonstrated by scientific studies. Use of on-farm written protocols for mastitis treatment promotes a judicious use of antimicrobials and reduces the use of antimicrobials.

Treatment of mastitis during lactation

PubMed Central

2009-01-01

Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, because of high treatment costs and generally poor efficacy. All mastitis treatment should be evidence-based, i.e., the efficacy of each product and treatment length should be demonstrated by scientific studies. Use of on-farm written protocols for mastitis treatment promotes a judicious use of antimicrobials and reduces the use of antimicrobials. PMID:22081939

Antimicrobial nanocomposites based on natural modified materials: a review of carbons and clays.

PubMed

Martynková, Grazyna Simha; Valásková, Marta

2014-01-01

The review is focused on the recent research and development of antimicrobial nanocomposites based on selected carbon nanomaterials and natural nanoclay minerals. The nanocomposites comprised of two or several components, where at least one presents antimicrobial properties, are discussed. Yet the most popular agent remains silver as nanoparticle or in ionic form. Second, broadly studied group, are organics as additives or polymeric matrices. Both carbons and clays in certain forms possess antimicrobial properties. A lot of interest is put on to research graphene oxide. The low-environmental impact technologies-based on sustainable biopolymers have been studied. Testing of antimicrobial properties of nanomaterials is performed most frequently on E. coli and S. aureus bacterias.

Microbiologic Response to Treatment of Bacterial Vaginosis with Topical Clindamycin or Metronidazole

PubMed Central

Austin, M. N.; Beigi, R. H.; Meyn, L. A.; Hillier, S. L.

2005-01-01

To compare the frequencies, concentrations, and antimicrobial susceptibilities of vaginal microbes isolated from women with bacterial vaginosis (BV) before and after therapy, 119 nonpregnant women aged 18 to 45 with clinical and Gram stain evidence of BV were randomized to receive intravaginal clindamycin or metronidazole. Vaginal swabs were collected at baseline and 7 to 12 days, 35 to 45 days, and 70 to 90 days following therapy for quantitative vaginal culture. For the 99 women completing all four visits, statistical analyses were performed comparing differences in vaginal microflora between the two treatment arms and between visits in the same treatment group. Antimicrobial susceptibility testing using the agar dilution method was performed for anaerobic gram-negative rods. Although both therapies resulted in decreased colonization by Gardnerella vaginalis and Mycoplasma hominis, only metronidazole treatment resulted in a significant decrease in the frequency and concentration of Prevotella bivia and black-pigmented Prevotella species. Of the 865 anaerobic gram-negative rods evaluated for susceptibility, only 3 (0.3%) were resistant to metronidazole, whereas clindamycin resistance increased significantly for P. bivia and black-pigmented anaerobic gram-negative rods persisting following clindamycin therapy. Clindamycin-resistant subpopulations of P. bivia and black-pigmented Prevotella species emerged 7 to 12 days after therapy even among women colonized initially by clindamycin-susceptible strains. These resistant subpopulations persisted at high frequencies (42 to 50%) 70 to 90 days following therapy. The two topical agents for treatment of BV have differing microbiologic effects on the vaginal microflora. The emergence of clindamycin-resistant anaerobic gram-negative rods following therapy is of concern. PMID:16145097

Role of Ozone Therapy in Minimal Intervention Dentistry and Endodontics - A Review

PubMed Central

A, Shilpa Reddy; Reddy, Narender; Dinapadu, Sainath; Reddy, Manoranjan; Pasari, Srikanth

2013-01-01

Ozone has been successfully used in medical field since many years owing to its oxidizing property making it an excellent antimicrobial agent. Moreover its potent anti-inflammatory property along with favorable cellular and humoral immune response made ozone an effective therapeutic agent. Also its ability to arrest and reverse carious lesions in a predictable way opened up a new chapter in minimal intervention dentistry. Furthermore its efficacy in curbing resistant poly microbial root canal flora appears very promising. This article is based on information through valid textbooks, peer reviews, journals and medline/pubmed search. How to cite this article: Reddy S A, Reddy N, Dinapadu S, Reddy M, Pasari S. Role of Ozone Therapy in Minimal Intervention Dentistry and Endodontics - A Review. J Int Oral Health 2013; 5(3):102-108. PMID:24155611

Surgical management of corneal infections.

PubMed

Tuli, Sonal; Gray, Matthew

2016-07-01

The purpose of this review is to discuss the options for, and recent developments in, the surgical treatment of corneal infections. Although the mainstay of treatment of corneal infections is topical antimicrobial agents, surgical intervention may be necessary in a number of cases. These include advanced disease at presentation, resistant infections, and progressive ulceration despite appropriate treatment. Prompt and appropriate treatment can make the difference between a good outcome and loss of vision or the eye. There are a number of surgical therapies available for corneal infections. Preferred therapeutic modalities differ based on the size, causation, and location of the infection but consist of either replacement of the infected tissue or structural support of the tissue to allow healing. Although there are no completely novel therapies that have been developed recently, there have been incremental improvements in the existing treatment modalities making them more effective, easier, and safer. Several options are available for surgically managing corneal infections. Ophthalmologists should select the optimal procedure based on the individual patient's situation. http://links.lww.com/COOP/A20.

Surgical management of corneal infections

PubMed Central

Tuli, Sonal; Gray, Matthew

2016-01-01

Purpose of review The purpose of this review is to discuss the options for, and recent developments in, the surgical treatment of corneal infections. While the mainstay of treatment of corneal infections is topical antimicrobial agents, surgical intervention may be necessary in a number of cases. These include advanced disease at presentation, resistant infections, and progressive ulceration despite appropriate treatment. Prompt and appropriate treatment can make the difference between a good outcome and loss of vision or the eye. Recent findings There are a number of surgical therapies available for corneal infections. Preferred therapeutic modalities differ based on the size, causation, and location of the infection but consist of either replacement of the infected tissue or structural support of the tissue to allow healing. While there are no completely novel therapies that have been developed recently, there have been incremental improvements in the existing treatment modalities making them more effective, easier, and safer. Summary Several options are available for surgically managing corneal infections. Ophthalmologists should select the optimal procedure based on the individual patient’s situation. PMID:27096375

Systemic candidiasis in a cheetah (Acinonyx jubatus).

PubMed

La Perle, K M; Wack, R; Kaufman, L; Blomme, E A

1998-12-01

Systemic candidiasis, with involvement of the spleen, liver, kidneys, and lymph nodes, was diagnosed in a geriatric captive cheetah (Acinonyx jubatus). The animal had a long clinical history of intermittent chronic gastritis associated with Helicobacter acinonyx and chronic renal failure, both of which were repeatedly treated with broad-spectrum antimicrobial therapy. Following euthanasia, a postmortem examination showed numerous microabscesses and granulomas composed of degenerate eosinophils and containing asteroids or Splendore-Hoeppli material throughout the body. Yeast, pseudohyphae, and infrequently branching septate hyphae, demonstrated with special stains, were identified as a Candida sp. by fluorescent antibody testing. Low genetic variation in cheetahs may increase their susceptibility to infectious agents. Additional factors contributing to the overgrowth and dissemination of Candida sp. in this case may have included changes in the bacterial flora of the alimentary tract as a result of repeated antimicrobial therapy and alterations in the topography of the alimentary mucosa caused by chronic gastritis.

Synthetic membrane-targeted antibiotics.

PubMed

Vooturi, S K; Firestine, S M

2010-01-01

Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

A Review of Ten Years of the Study for Monitoring Antimicrobial Resistance Trends (SMART) from 2002 to 2011.

PubMed

Morrissey, Ian; Hackel, Meredith; Badal, Robert; Bouchillon, Sam; Hawser, Stephen; Biedenbach, Douglas

2013-11-01

Surveillance of antimicrobial agent resistance provides important information to guide microbiologists and infectious disease specialists understanding of the control and the spread of resistance mechanisms within the local environment. Continued monitoring of antimicrobial resistance patterns in the community and in local hospital environments is essential to guide effective empiric therapy. The Study for Monitoring Antimicrobial Resistance Trends (SMART) has monitored the in vitro susceptibility patterns of clinical Gram-negative bacilli to antimicrobial agents collected worldwide from intra-abdominal infections since 2002 and urinary tract infections since 2009. Resistance trends, with a particular focus on carbapenem resistance and the rate of extended-spectrum β-lactamases (ESBLs), were analyzed. Isolates from intra-abdominal infections (n = 92,086) and urinary-tract infections (n = 24,705) were collected and tested using Clinical and Laboratory Standards Institute methods. This review presents carbapenem susceptibility and ESBL rates over ten years of SMART study analysis, including key publications during this period. The SMART study has proved to be a valuable resource in determining pathogen prevalence and antibiotic susceptibility over the last ten years and continues to provide evidence for regulatory susceptibility breakpoints and clinical decision making.

A Systematic Review of the Definitions, Determinants, and Clinical Outcomes of Antimicrobial De-escalation in the Intensive Care Unit.

PubMed

Tabah, Alexis; Cotta, Menino Osbert; Garnacho-Montero, Jose; Schouten, Jeroen; Roberts, Jason A; Lipman, Jeffrey; Tacey, Mark; Timsit, Jean-François; Leone, Marc; Zahar, Jean Ralph; De Waele, Jan J

2016-04-15

Antimicrobial de-escalation (ADE) is a strategy to reduce the spectrum of antimicrobials and aims to prevent the emergence of bacterial resistance. We present a systematic review describing the definitions, determinants and outcomes associated with ADE. We included 2 randomized controlled trials and 12 cohort studies. There was considerable variability in the definition of ADE. It was more frequently performed in patients with broad-spectrum and/or appropriate antimicrobial therapy (P= .05 to .002), when more agents were used (P= .002), and in the absence of multidrug-resistant pathogens (P< .05). Where investigated, lower or improving severity scores were consistently associated with ADE (P= .04 to <.001). The pooled effect of ADE on mortality is protective (relative risk, 0.68; 95% confidence interval, .52-.88). Because the determinants of ADE are markers of clinical improvement and/or of lower risk of treatment failure this effect on mortality cannot be retained as evidence. None of the studies were designed to investigate the effect of ADE on antimicrobial resistance. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Improving patient care through implementation of an antimicrobial stewardship program.

PubMed

Palmer, Hannah R; Weston, Jaye; Gentry, Layne; Salazar, Miguel; Putney, Kimberly; Frost, Craig; Tipton, Joyce A; Cottreau, Jessica; Tam, Vincent H; Garey, Kevin W

2011-11-15

The implementation of an antimicrobial stewardship program at a health system is described. In 2008, the Center for Antimicrobial Stewardship and Epidemiology (CASE) was formed at St. Luke's Episcopal Hospital (SLEH) to improve the quality of care for patients as it related to antimicrobial therapy. The charter of CASE contained specific aims for improving patient care, furthering clinical research, and training the next generation of clinical infectious diseases pharmacists. The CASE team consists of at least two infectious diseases pharmacists and one physician (the medical director) who provide direct oversight for antimicrobial utilization within the hospital. The CASE medical director, an infectious diseases physician, is responsible for overseeing the activities of the center. With the oversight of the CASE advisory board, the medical director develops and implements the antimicrobial stewardship and management policies for SLEH. Another key innovative feature of CASE is its extensive involvement in training new infectious diseases pharmacists and conducting research. CASE uses a model in which a clinical scenario or problem is identified, a research project is undertaken to further elucidate the problem, and policy changes are made to improve patient outcomes. The CASE team is supported by a CASE advisory board, a CASE research collaborative including university faculty, and a dedicated training program for pharmacy fellows, residents, and students. Implementation of an antimicrobial stewardship program at a health system helped decrease the inappropriate use of antibiotics, improve patient care and outcomes, further clinical research, and increase training opportunities for future clinical infectious diseases pharmacists.

Urinary Tract Infection: Pathogenesis and Outlook.

PubMed

McLellan, Lisa K; Hunstad, David A

2016-11-01

The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy of direct Gram stain in differentiating staphylococci from streptococci in blood cultures positive for gram-positive cocci.

PubMed Central

Agger, W A; Maki, D G

1978-01-01

A preponderance of clusters seen on direct Gram stain of blood cultures positive for gram-positive cocci was 98% sensitive and 100% specific for identification of staphylococcal species or of Peptococcus. A preponderance of chains, pairs, or both was 100% sensitive and 98% specific for identifying streptococci. Further presumptive identification of either staphylococci or streptococci based on microscopic morphology was unreliable. The direct Gram stain is highly reliable for differentiating staphylococci from streptococci and should be of considerable value to clinicians selecting initial antimicrobial therapy. PMID:75888

Clinical Study of Bacillus coagulans Unique IS-2 (ATCC PTA-11748) in the Treatment of Patients with Bacterial Vaginosis.

PubMed

Ratna Sudha, M; Yelikar, Kanan A; Deshpande, Sonali

2012-09-01

Bacterial vaginosis (BV) is the most prevalent vaginal infection worldwide and is characterized by reduction of native lactobacilli. Antimicrobial therapy used to cure the disease is often found to be ineffective. We postulate that Bacillus coagulans Unique IS-2 (Unique Biotech Limited, India) might provide an appendage to antimicrobial treatment and improve curing rate. In the present study 40 Indian women diagnosed with BV by the presence of symptoms including white discharge, pH greater than 4.7, burning micturation, itching, soreness and redness at vulva. The subjects were divided in 2 groups probiotic (n = 20) and control (n = 20) based on age (control group, 33 ± 3 years and probiotic group, 32.5 ± 3 years), history of previous vaginosis (control group, 75% or 15/20 and probiotic group, 75% or 15/20) and severity of current vaginosis infection (burning micturation and itching, 35% in each group). Probiotic group subjects were assigned to receive a dose of antibiotic therapy [Ofloxacin-Ornidazole with strength of 200-500 mg per capsule/day for 5 days along with vaginal peccaries (co-kimaxazol) for 3 days] simultaneously with two probiotic capsules (10(9) CFUs of Bacillus coagulans Unique IS-2 per capsule). The control group received only antibiotic therapy. At the end of the treatment the 80% of probiotic group subjects showed significant positive response as revealed by reduction of vaginosis symptoms compared to the control group which exhibited reduction in 45% subjects only. Thus, the results of present study indicate that strain Bacillus coagulans Unique IS-2 can provide benefits to women being treated with antibiotics to cure an infectious condition.

The presence of urinary nitrites is a significant predictor of pediatric urinary tract infection susceptibility to first- and third-generation cephalosporins.

PubMed

Weisz, Dany; Seabrook, Jamie A; Lim, Rodrick K

2010-07-01

Previous studies in adults have refuted the use of nitrites as a predictor of bacterial resistance to both trimethoprim-sulfamethoxazole and cephalosporins. Some centers now consider first-line outpatient therapy with an oral third-generation cephalosporin appropriate for young children. The objective of this study was to determine if nitrite-negative pediatric urinary tract infections (UTIs) were more likely than nitrite-positive UTIs to be resistant to cephalosporins. This may enable physicians to adjust antimicrobial therapy before patients leave the Emergency Department (ED) to avoid the complications of ineffectively treated pediatric UTIs. A retrospective chart review examined, over a 9-month period, 173 pediatric patients who were diagnosed with a clinical UTI in the ED and who also had a positive urine culture and a recorded dipstick at the time of visit. The chi-squared test and Fisher's exact test were used to compare nitrite-negative vs. nitrite-positive UTIs for resistance to third-generation cephalosporins and other empiric antimicrobials. For third-generation cephalosporins, 1.4% of nitrite-positive UTIs were resistant, whereas 14.4% of nitrite-negative UTIs were resistant (95% confidence interval [CI] -0.22 to -0.05). For first-generation cephalosporins, 8.4% were resistant in the nitrite-positive group, compared to 22.2% in the nitrite-negative group (95% CI -0.24 to -0.03). The absence of urinary nitrites is a significant indicator for potential resistance to cephalosporins in pediatric UTIs. Due to low levels of pediatric UTI resistance, cephalosporins continue to represent useful empiric therapy in the general pediatric population. However, in high-risk patients, physicians may opt to alter their empiric choice of antibiotic based on the presence of urinary nitrites. Copyright 2010 Elsevier Inc. All rights reserved.

[Domiciliary parenteral antibiotic therapy: a prospective analysis of the last 12 years].

PubMed

Peláez Cantero, M J; Madrid Rodríguez, A; Urda Cardona, A L; Jurado Ortiz, A

2014-08-01

Parenteral antibiotic treatment has been classically developed in hospitals and is considered as a hospital procedure. The development of Hospital at Home Units (HHU) has led to an increase in outpatient parenteral antibiotic therapy (OPAT) in paediatrics patients. The objective of this study is to describe our experience, as an HHU integrated within a Paediatric Department, in home antimicrobial therapy over a period of 12 years. This prospective and descriptive study included every patient with a disease requiring parenteral antimicrobial therapy who was admitted to our HHU from January 2000 to December 2012. During the study there were 163 cases on OPAT. The mean age of the patients was 11.1 years, and the sample group was comprised of 33 males and 22 feamales. The main sources of the treated infections were respiratory tract (76%), catheter-related bloodstream (9.2%), and urinary tract infections (5.5%). Amikacin was the most widely used antibiotic. Almost all treatments (96.6%) were via an intravenous route. Catheter-associated complications were more common than drug-associated complications. Successful at-home treatment was observed in 90.2% of cases. OPAT is a good and safe alternative in many paediatric diseases. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Effect of surgical periodontal treatment associated to antimicrobial photodynamic therapy on chronic periodontitis: A randomized controlled clinical trial.

PubMed

Martins, Sérgio H L; Novaes, Arthur B; Taba, Mario; Palioto, Daniela B; Messora, Michel R; Reino, Danilo M; Souza, Sérgio L S

2017-07-01

This randomized controlled clinical trial evaluated the effects of an adjunctive single application of antimicrobial photodynamic therapy (aPDT) in Surgical Periodontal Treatment (ST) in patients with severe chronic periodontitis (SCP). In a split-mouth design, 20 patients with SCP were treated with aPDT+ST (Test Group, TG) or ST only (Control Group, CG). aPDT was applied in a single episode, using a diode laser and a phenothiazine photosensitizer. All patients were monitored until 90 days after surgical therapy. Levels of 40 subgingival species were measured by checkerboard DNA-DNA hybridization at baseline, 60 and 150 days. Clinical and microbiological parameters were evaluated. In deep periodontal pockets depth (PPD ≥5 mm), Test Group presented a significantly higher decrease in PPD than Control Group at 90 days after surgical therapy (p < .05). Test Group also demonstrated significantly less periodontal pathogens of red complex (Treponema denticola) (p < .05). A single episode of aPDT used in adjunct to open flap debridement of the root surface in the surgical treatment of SCP: i) significantly improved clinical periodontal parameters; ii) eliminates periodontal pathogens of the red complex more effectively (NCT02734784). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diversity of Staphylococcus pseudintermedius in carriage sites and skin lesions of dogs with superficial bacterial folliculitis: potential implications for diagnostic testing and therapy.

PubMed

Larsen, Rikke Friis; Boysen, Lene; Jessen, Lisbeth Rem; Guardabassi, Luca; Damborg, Peter

2018-05-21

Staphylococcus pseudintermedius is genotypically diverse within the canine population and multiple strains may colonize individual dogs at any given time. If multiple strains with distinct antimicrobial resistance profiles are present in superficial bacterial folliculitis (SBF), sampling a single skin lesion for culture and antimicrobial susceptibility testing (AST) might be inadequate to select effective therapy. To investigate S. pseudintermedius diversity in carriage sites and lesions of dogs with SBF. Fourteen dogs with SBF. Staphylococcus pseudintermedius isolates obtained from perineum, gingiva and four to six skin lesions per dog were subjected to pulsed-field gel electrophoresis (PFGE) and AST to assess diversity between lesions. For two dogs, 14-16 isolates per lesion were included in the analysis to assess diversity within lesions. Analysis of one isolate per lesion revealed one to four strains displaying unique PFGE profiles, and up to three unique antimicrobial resistance (AMR) profiles for each dog. Multiple pustules from the same dog always harboured the same strain, whereas papules, crusts and collarettes did not. Up to four strains with distinct AMR profiles were isolated from the same lesion in two dogs. In 12 dogs, at least one carriage site strain also was represented in lesions. Lesions of SBF may harbour multiple S. pseudintermedius strains with distinct antimicrobial resistance profiles. Pustules are the best target for bacterial culture. It remains unclear whether isolation of different strains from other lesion types is a consequence of contamination or co-infection by multiple strains. © 2018 ESVD and ACVD.

Taking an Antibiotic Time-out: Utilization and Usability of a Self-Stewardship Time-out Program for Renewal of Vancomycin and Piperacillin-Tazobactam.

PubMed

Graber, Christopher J; Jones, Makoto M; Glassman, Peter A; Weir, Charlene; Butler, Jorie; Nechodom, Kevin; Kay, Chad L; Furman, Amy E; Tran, Thuong T; Foltz, Christopher; Pollack, Lori A; Samore, Matthew H; Goetz, Matthew Bidwell

2015-11-01

Antibiotic time-outs can promote critical thinking and greater attention to reviewing indications for continuation. We pilot tested an antibiotic time-out program at a tertiary care teaching hospital where vancomycin and piperacillin-tazobactam continuation past day 3 had previously required infectious diseases service approval. The time-out program consisted of 3 components: (1) an electronic antimicrobial dashboard that aggregated infection-relevant clinical data; (2) a templated note in the electronic medical record that included a structured review of antibiotic indications and that provided automatic approval of continuation of therapy when indicated; and (3) an educational and social marketing campaign. In the first 6 months of program implementation, vancomycin was discontinued by day 5 in 93/145 (64%) courses where a time-out was performed on day 4 versus in 96/199 (48%) 1 year prior (P = .04). Seven vancomycin continuations via template (5% of time-outs) were guideline-discordant by retrospective chart review versus none 1 year prior (P = .002). Piperacillin-tazobactam was discontinued by day 5 in 70/105 (67%) courses versus 58/93 (62%) 1 year prior (P = .55); 9 continuations (9% of time-outs) were guideline-discordant versus two 1 year prior (P = .06). A usability survey completed by 32 physicians demonstrated modest satisfaction with the overall program, antimicrobial dashboard, and renewal templates. By providing practitioners with clinical informatics support and guidance, the intervention increased provider confidence in making decisions to de-escalate antimicrobial therapy in ambiguous circumstances wherein they previously sought authorization for continuation from an antimicrobial steward.

Quantitative cultures of bronchoscopically obtained specimens should be performed for optimal management of ventilator-associated pneumonia.

PubMed

Baselski, Vickie; Klutts, J Stacey; Baselski, Vickie; Klutts, J Stacey

2013-03-01

Ventilator-associated pneumonia (VAP) is a leading cause of health care-associated infection. It has a high rate of attributed mortality, and this mortality is increased in patients who do not receive appropriate empirical antimicrobial therapy. As a result of the overuse of broad-spectrum antimicrobials such as the carbapenems, strains of Acinetobacter, Enterobacteriaceae, and Pseudomonas aeruginosa susceptible only to polymyxins and tigecycline have emerged as important causes of VAP. The need to accurately diagnose VAP so that appropriate discontinuation or de-escalation of antimicrobial therapy can be initiated to reduce this antimicrobial pressure is essential. Practice guidelines for the diagnosis of VAP advocate the use of bronchoalveolar lavage (BAL) fluid obtained either bronchoscopically or by the use of a catheter passed through the endotracheal tube. The CDC recommends that quantitative cultures be performed on these specimens, using ≥ 10(4) CFU/ml to designate a positive culture (http://www.cdc.gov/nhsn/TOC_PSCManual.html, accessed 30 October 2012). However, there is no consensus in the clinical microbiology community as to whether these specimens should be cultured quantitatively, using the aforementioned designated bacterial cell count to designate infection, or by a semiquantitative approach. We have asked Vickie Baselski, University of Tennessee Health Science Center, who was the lead author on one of the seminal papers on quantitative BAL fluid culture, to explain why she believes that quantitative BAL fluid cultures are the optimal strategy for VAP diagnosis. We have Stacey Klutts, University of Iowa, to advocate the semiquantitative approach.

Mycobacterial r32-kDa antigen-specific T-cell responses correlate with successful treatment and a heightened anti-microbial response in human leprosy patients.

PubMed

Neela, Venkata Sanjeev Kumar; Devalraju, Kamakshi Prudhula; Pydi, Satya Sudheer; Sunder, Sharada Ramaseri; Adiraju, Kameswara Rao; Singh, Surya Satyanarayana; Anandaraj, M P J S; Valluri, Vijaya Lakshmi

2016-09-01

Immunological characterization of mycobacterial peptides may help not only in the preparation of a vaccine for leprosy but also in developing in vitro T-cell assays that could perhaps be used as an in vitro correlate for treatment outcome. The main goal of this study was to evaluate the use of Mycobacterium bovis recombinant 32-kDa protein (r32-kDa) antigen-stimulated T-cell assay as a surrogate marker for treatment outcome and monitor vitamin D receptor (VDR)-mediated anti-microbial responses during multidrug therapy (MDT) in leprosy. Newly diagnosed tuberculoid and lepromatous leprosy patients were enrolled and followed up during their course of MDT at 6 and 12 months. IFN-γ, IL-10, IL-17 and IL-23 levels in culture supernatants and expression of VDR, TLR2, LL37 and DEFB in r32-kDa-stimulated PBMCs were measured. Controls comprised household contacts (HHCs) and healthy endemic subjects (HCs). Significant differences were observed in the levels of IFN-γ, IL-17, IL-23, VDR and anti-microbial peptides LL37 and DEFB after treatment and when compared with that of HHCs and HCs, respectively. These findings suggest that responses to r32-kDa antigen reflect an improved immunological and anti-microbial response in leprosy patients during therapy, thereby indicating its potential use as an immune correlate in the treatment of leprosy patients. © The Japanese Society for Immunology. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Imipenem/cilastatin encapsulated polymeric nanoparticles for destroying carbapenem-resistant bacterial isolates.

PubMed

Shaaban, Mona I; Shaker, Mohamed A; Mady, Fatma M

2017-04-11

Carbapenem-resistance is an extremely growing medical threat in antibacterial therapy as the incurable resistant strains easily develop a multi-resistance action to other potent antimicrobial agents. Nonetheless, the protective delivery of current antibiotics using nano-carriers opens a tremendous approach in the antimicrobial therapy, allowing the nano-formulated antibiotics to beat these health threat pathogens. Herein, we encapsulated imipenem into biodegradable polymeric nanoparticles to destroy the imipenem-resistant bacteria and overcome the microbial adhesion and dissemination. Imipenem loaded poly Ɛ-caprolactone (PCL) and polylactide-co-glycolide (PLGA) nanocapsules were formulated using double emulsion evaporation method. The obtained nanocapsules were characterized for mean particle diameter, morphology, loading efficiency, and in vitro release. The in vitro antimicrobial and anti adhesion activities were evaluated against selected imipenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa clinical isolates. The obtained results reveal that imipenem loaded PCL nano-formulation enhances the microbial susceptibility and antimicrobial activity of imipenem. The imipenem loaded PCL nanoparticles caused faster microbial killing within 2-3 h compared to the imipenem loaded PLGA and free drug. Successfully, PCL nanocapsules were able to protect imipenem from enzymatic degradation by resistant isolates and prevent the emergence of the resistant colonies, as it lowered the mutation prevention concentration of free imipenem by twofolds. Moreover, the imipenem loaded PCL eliminated bacterial attachment and the biofilm assembly of P. aeruginosa and K. pneumoniae planktonic bacteria by 74 and 78.4%, respectively. These promising results indicate that polymeric nanoparticles recover the efficacy of imipenem and can be considered as a new paradigm shift against multidrug-resistant isolates in treating severe bacterial infections.